1-s2.0-S0168170214002640-main (1)
Virus Research 190(2014)75–96
Contents lists available at ScienceDirect
Virus
Research
j o u r n a l h o m e p a g e :w w w.e l s e v i e r.c o m /l o c a t e /v i r u s r e
s
Review
Rotaviruses
Ulrich Desselberger ?
Department of Medicine,University of Cambridge,Addenbrooke’s Hospital,Cambridge CB20QQ,UK
a r t i c l e
i n f o
Article history:
Received 8May 2014
Received in revised form 26June 2014Accepted 26June 2014
Available online 9July 2014
Keywords:Rotavirus
Structure–function studies Replication cycle Pathogenesis
Immune responses and correlates of protection
Prevention by vaccination
a b s t r a c t
Recent advances of rotavirus (RV)basic and applied research are reviewed.They consist of determination of the RV particle structure and functions of structural proteins,classi?cation into genotypes based on whole genome analyses,description of the RV genome and gene protein assignments,description of the viral replication cycle and of functions of RV-encoded non-structural proteins as well as cellular pro-teins and cellular organelles involved,the present status of RV genetics and reverse genetics,molecular determinants of pathogenesis and pathophysiology,the RV-speci?c humoral and cell-mediated immune responses,innate immune responses and correlates of protection,laboratory diagnosis,differential diag-nosis and present status of treatment,the molecular epidemiology and mechanisms of evolution of RVs,the development and universal application of RV vaccines as well as issues arising from present universal RV vaccination programs and work on alternative vaccines.The review concludes by presenting problems requiring further exploration and perspectives of future basic and translational research.
?2014The Authors.Published by Elsevier B.V.This is an open access article under the CC BY-NC-ND
license (https://www.360docs.net/doc/c88711488.html,/licenses/by-nc-nd/3.0/).
Contents
1.Introduction ..........................................................................................................................................76
2.Structure ..............................................................................................................................................76
3.Classi?cation ..........................................................................................................................................76
4.The rotavirus genome and gene-protein assignments ...............................................................................................78
5.
The rotavirus replication cycle .......................................................................................................................785.1.Virus particle attachment .....................................................................................................................785.2.Virus particle penetration and uncoating ....................................................................................................795.3.RV plus strand (m)RNA synthesis .............................................................................................................795.4.Viroplasm formation ..........................................................................................................................805.5.RNA packaging,minus strand RNA synthesis and DLP formation............................................................................815.6.Virus particle (virion)maturation and release ...............................................................................................815.7.Persistent RV infection ........................................................................................................................815.8.Growth of RVs in stem cell organoids ........................................................................................................815.9.Cellular proteins involved in RV replication ..................................................................................................816.RV genetics and reverse genetics .....................................................................................................................827.Molecular pathogenesis and pathophysiology .......................................................................................................828.Immune responses ...................................................................................................................................
838.1.RV-speci?c humoral and cell-mediated immune responses .................................................................................838.2.Innate immune responses ....................................................................................................................848.3.Correlates of protection .......................................................................................................................849.Clinical symptoms and differential diagnosis,laboratory diagnosis and treatment ................................................................8410.Molecular epidemiology and mechanisms of evolution ............................................................................................8511.Prevention:development and universal application of RV vaccines,issues arising from present RV vaccination programs .....................8612.Perspectives of future basic and translational research ............................................................................................
87
?Tel.:+441223763403;fax:+441223336846.E-mail address:ud207@https://www.360docs.net/doc/c88711488.html,
https://www.360docs.net/doc/c88711488.html,/10.1016/j.virusres.2014.06.016
0168-1702/?2014The Authors.Published by Elsevier B.V.This is an open access article under the CC BY-NC-ND license (https://www.360docs.net/doc/c88711488.html,/licenses/by-nc-nd/3.0/).
76U.Desselberger/Virus Research190(2014)75–96
Acknowledgements (87)
References (87)
1.Introduction
Rotaviruses(RVs)were recognized as a major cause of acute gas-troenteritis(AGE)in infants and young children in1973(Bishop et al.,1973;Flewett et al.,1973).Before that year RVs had already been discovered in diarrheic mice(Adams and Kraft,1963), monkeys(Malherbe and Harwin,1963)and cattle(Mebus et al., 1969)and since then in the young of many mammalian species including bats(Estes and Greenberg,2013;He et al.,2013)and also in birds(Kindler et al.,2013;Otto et al.,2012;Trojnar et al.,2009). During the last40years an enormous amount of basic research on RV structure,replication,pathogenesis and immune responses has accumulated.Due to modern diagnostic techniques the molecular epidemiology of RVs has been extensively explored.Recently,two live attenuated RV vaccines have been licensed in many countries and are increasingly being applied in universal vaccination pro-grams.In the following I will attempt to give an up-to-date review of important recent achievements in research and prevention and to formulate remaining open questions and perspectives.
2.Structure
The fully infectious RV particle(=virion)consists of3protein layers and is also termed triple-layered particle(TLP).By electron microscopy,TLPs resemble wheels(lat.rota),and this appearance has led to the name of Rotavirus for the genus(Flewett et al.,1974). Based on cryo-electron microscopy and image reconstruction data (reviewed by Jayaram et al.,2004),the following structure of icosa-hedral symmetry has been recognized:the single layered particle (SLP=core shell)is formed by120molecules of the viral protein 2(VP2),arranged as60dimers in a T=1symmetry(Fig.1C).Five of the dimers form a decamer around the?vefold symmetry axis, and12decamers make up the core protein layer which is uniform except for small pores along the?vefold axis(McClain et al.,2010). A‘?vefold hub’(density)projecting into the core interior along the ?vefold axis was?rst thought to be contributed by the N-terminus of VP2(McClain et al.,2010),but was more recently recognized to result from the VP1structure(Estrozi et al.,2013).Replication enzyme complexes,consisting of VP1and VP3,are located at the inside of the core at the axis of?vefold symmetry(Fig.1C and D)opposite the class I channels(McClain et al.,2010;Trask et al., 2012a,2012b;Estrozi et al.,2013)and are in intense contact with one particular dedicated genomic dsRNA segment via VP1(Periz et al.,2013).The core shell encloses the viral genome of11seg-ments of dsRNA as well as the viral RNA dependent RNA polymerase (RdRp),VP1and the capping enzyme,VP3.
The genomic RNA segments have been proposed to form conical cylinders around the replication complexes(Prasad et al., 1996;Jayaram et al.,2004)(Fig.1D)but details of the dsRNA structure within the core are just beginning to be explored.Thus, in actively transcribing double-layered particles(DLPs,see below), a decreased order of the middle(VP6)layer was found to be accom-panied by increased order of the core content(Kam et al.,2014). Similar partial order of dsRNA segments was observed in core par-ticles of bluetongue virus(Gouet et al.,1999).The11RNA segments (Fig.1A)have very short completely conserved5 and3 terminal nucleotide(nt)sequences,5 -GGC···ACC-3 .The untranslated regions(UTR)of the RNA segments(+sense)are small:9–48nt at the5 end,and17–182nt at the3 end.The5 and3 ends are of partial inverted complementarity and are subject to long range interactions(LRI)(Tortorici et al.,2006;Li et al.,2010).Those at the 3 end function as RdRp recognition signals(Tortorici et al.,2003) and also interact with NSP3(Chizhikov and Patton,2000;Vende et al.,2000),involved in activation of translation(see below).The RdRp structure has been solved at a resolution of2.9?A(Lu et al., 2008)(Fig.2):VP1forms a cage-like structure disrupted by4 tunnels(leading to the catalytic site in the center of the molecule) which are proposed to allow for:(1)the entry of free nucleoside triphosphates(NTPs),(2)the entry of template ssRNA,(3)the exit of the(+)ssRNA product,and(4)the exit of(?)ssRNA(transcrip-tion)or dsRNA(replication).Tunnel3is positioned toward the class I channel inside of VP2(Settembre et al.,2011;Estrozi et al., 2013),permitting release of(+)RNAs into the cytoplasm;tunnel 4directs the newly replicated dsRNA toward the core interior. Analysis of different VP1-polyribo-oligonucleotide complexes has resulted in the?nding that the5 -UGUG-3 sequence at the3 end of the RNA is speci?cally recognized at the template entry channel (Lu et al.,2008).In many aspects the structure of the RV RdRp is similar to the corresponding enzyme of orthoreovirus(Tao et al., 2002).
The viral core is surrounded by260trimers of VP6,which form the middle layer and constitute double-layered particles (DLPs)(Fig.1C and E).The VP6structure has also been determined (Mathieu et al.,2001):VP6trimers make contact with both the underlying core(VP2)(Charpilienne et al.,2002)as well as VP7and VP4trimers on the outside.
The DLPs in turn are covered by260trimers of VP7and60 spikes of VP4trimers(=180molecules)to form the TLPs(Fig.1B and C).The virions contain132channels along the axes of?ve-fold(12channels of class I),threefold and twofold symmetry(60 class II and60class III channels,respectively)(Jayaram et al.,2004). The three-dimensional(3D)structure of the RV virion has recently been determined by electron cryomicroscopy(cryoEM)and single-particle tomography at about4.3?A resolution(Settembre et al., 2011):there is an intense interaction of the VP4trimer with both VP6(into which the base of VP5*is half buried)and VP7 (Fig.3).The structure and interactions of VP4with other struc-tural RV proteins permit the description of a mechanism of RV entry(see below).It has previously been shown that VP4trimers can only be observed by cryo-EM in TLPs grown in the pres-ence of trypsin(Crawford et al.,2001).Since the stoichiometry of VP4in RVs grown in the presence and absence of trypsin is identical,it was concluded that VP4spikes of RV grown in the absence of trypsin are icosahedrally disordered.By single particle cryo-EM and cryo-electron tomography(cryo-ET)it has recently been demonstrated for2RV strains that the VP4spike structure of RV particles grown in the absence of trypsin is indistinguishable from that of particles grown in the presence of trypsin(Rodríguez et al.,2014),suggesting that the previous lack of observation of VP4 structures in trypsin-free grown RV particles was mainly due to the imposition of icosahedral structure requirements on the previous cryo-EM data and that proteolytic cleavage of VP4mainly achieves conformational changes enabling viral entry into cells.As an aside, the science of structural biology is closely related to talents in visual arts as noted by Stephen and Baumeister(2008).
3.Classi?cation
Rotaviruses constitute the genus Rotavirus,one of the15genera of Reoviridae family which is subdivided into the sub-families of
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Fig.1.Aspects of rotavirus structure.(A)PAGE gel showing 11dsRNA segments comprising the rotavirus (RVA)genome.The gene segments are numbered on the left and the proteins they encode are indicated on the right.(B)Cryo-EM reconstruction of the rotavirus triple-layered particle.The spike protein VP4is colored in orange and the outermost VP7layer in yellow.(C)A cutaway view of the rotavirus TLP showing the inner VP6(blue)and VP2(green)layers and the transcriptional enzymes (in red)anchored to the inside of the VP2layer at the ?vefold axes.(D)Schematic depiction of genome organization in rotavirus.The genome segments are represented as inverted conical spirals surrounding the transcription enzymes (shown as red balls)inside the VP2layer in green.(E and F)Model from Cryo-EM reconstruction of transcribing DLPs.The endogenous transcription results in the simultaneous release of the transcribed mRNAs from channels located at the ?vefold vertices of the icosahedral DLP.
From Jayaram et al.(2004).With permission of the authors and the
publisher.
Fig.2.Structure of the RV RdRp VP1.Surface rendering (A)of the complete VP1polypeptide chain.The N-terminal domain is in yellow,the C-terminal (bracelet)domain is in pink,and the C-terminal plug is in cyan.(B)Sagittal cutaway of the image in (A),after rotation to the left by 90?,showing the four tunnels extending into the central cavity.
From Lu et al.(2008).With permission of the authors and the publisher.
the Sedoreovirinae (genera Cardoreovirus ,Mimoreovirus ,Orbivirus ,Phytoreovirus ,Rotavirus ,Seadornavirus )and the Spinareovirinae (genera Aquareovirus ,Coltivirus ,Cypovirus ,Dinovernavirus ,Fijivirus ,Idnoreovirus ,Mycoreovirus ,Orthoreovirus ,Oryzavirus ).According to the serological reactivity and genetic variability of VP6,at least 8different groups,also termed species,are differentiated (termed RVA-RVH)(Matthijnssens et al.,2012).The RVA species comprises at least 27G types (according to the nt sequence of VP7)and 37P types (according to the nt sequence of VP4)(Matthijnssens et al.,2011a;Rotavirus Classi?cation Working Group,2013).For G types,serotypes and genotypes are synony-mous,e.g.G1,G2,etc.For P types,there are many more P genotypes
than reference sera determining P serotypes:therefore,a double nomenclature has been introduced,e.g.P1A[8]designating the P serotype 1A and P genotype 8,etc.(Estes and Greenberg,2013).A comprehensive,nt sequence-based classi?cation comprising the complete genome has been introduced for RVAs,in which the VP7–VP4–VP6–VP1–VP2–VP3–NSP1–NSP2–NSP3–NSP4–NSP5/6genotypes are identi?ed and differentiated according to particular cut-off points of nt sequence identities (Matthijnssens et al.,2008a,2008b,2011a;Maes et al.,2009).Table 1demonstrates the enormous degree of genomic diversity among RVAs co-circulating in different population groups and animals at various times.Recently,similar comprehensive genotype differentiations for
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Fig.3.Interaction of rotavirus structural proteins.Cutaway view of the interactions of VP4within the TLP.VP8*is in magenta and VP5*is in red.The VP5*segment that will form the coiled coil(c-c)in the‘post-entry’conformation is in cyan.The globular foot domains of the VP5*is anchored at a six-coordinated position in the VP6layer(green);a VP7trimer(yellow)caps each trimer of VP6.Both form surface lattices in T=13levo icosahedral symmetry.The VP6lattice overlays the VP2shell (dark blue),which surrounds the coiled RNA genome(not shown).
From Settembre et al.(2011).With permission of the authors and the publisher. Table1
Genotypes of species A rotaviruses.
RV protein Percent
identity a Number of
genotypes b
Genotype(acronym
underlined)
VP78027G Glycosylated
VP48037P Protease-sensitive
VP68518I Inner capsid
VP1839R RdRp c
VP2849C Core protein
VP3818M Methyltransferase
NSP17919A Interferon Antagonist NSP28510N NTPase
NSP38512T Translation enhancer NSP48515E Enterotoxin
NSP59111H PHosphoprotein
Updated from Matthijnssens et al.(2008a,2008b).
a Nucleotide percent identity cut off value de?ning genotypes.
b October2013(Rotavirus Classi?cation Working Group,6th meeting,Valencia/ Spain).
c RNA-dependent RNA polymerase.
RVBs and RVCs have started to be established(Marthaler et al., 2012,2013).
4.The rotavirus genome and gene-protein assignments
The RVA genome is approximately18,500bp in size and con-sists of11segments of dsRNA which encode6structural and6 non-structural proteins.The genes are monocistronic,except for genome segment11,which encodes two proteins.The gene seg-ments are between667and3302bp in length.The gene-protein and protein-function assignments have been determined for sev-eral RVA strains and are shown for the bovine RVA RF(G6P6[1]) strain in Table2.Besides the6structural proteins described above(VP1,VP2,VP3,VP4,VP6,VP7),5–6non-structural pro-teins(NSP1–NSP5/6)are produced the functions of which will be described below.RVCs do not encode an NSP6.
The differences at the3 end of the RNAs between different RV species are considered to be the reason for their lack of reassort-ment(see below).The short5 and3 UTRs are not long enough to singly contain the putative packaging sequences important for RV morphogenesis,but direct experimental evidence is so far missing due to the lack of a tractable reverse genetics system for RVs(see below).The packaging signals of the RNA segments of in?uenza viruses and as far as explored of the orbiviruses include sequences of parts of the UTRs and the adjacent ORFs(Essere et al.,2013; Matsuo and Roy,2009).
Rotavirus genes can be‘rearranged’,due to partial nt duplica-tions or deletions of RNA segments generated by special forms of intragenic recombination(Desselberger,1996).Rotaviruses with rearrangements in3genes were found to package approximately 1800additional bp of RNA,i.e.about10%of the genome,to be replication competent and to be physically and genetically stable (Hundley et al.,1987;McIntyre et al.,1987).Genome rearrange-ments can be experimentally reproduced by serial passage of RVs in cell culture at high MOI(Hundley et al.,1985).
5.The rotavirus replication cycle
The RV replication cycle(Fig.4)includes the following steps: -attachment,mediated by VP4and VP7
-penetration and uncoating
-plus strand ssRNA(=mRNA)synthesis,mediated by VP1,VP3and VP2
-viroplasm formation,mediating RNA packaging,minus strand RNA synthesis(=RNA replication)and DLP formation
-Virus particle maturation(to TLPs)and release
5.1.Virus particle attachment
RV attachment is a complex process(López and Arias,2004). First,the infectious RV particle,the TLP,interacts by its VP4 spikes with cellular receptors(attachment receptors).The recep-tors contain sialic acid(SA)in terminal or sub-terminal positions. For the rhesus RV VP4the SA binding site has been structurally identi?ed(Dormitzer et al.,2002a,2002b).Treatment of cells by neuraminidase abolishes infection by certain RV strains(e.g.SA11) which have therefore been called SA-sensitive strains(Isa et al., 2006).Other strains which can infect neuraminidase-treated cells, have initially been termed‘SA-resistant’strains(e.g.Wa and DS-1) but were then shown to bind to receptors containing SA in inter-nal position of glycolipids which are insensitive to neuraminidase treatment,e.g.the GM1ganglioside(Guo et al.,1999;Haselhorst et al.,2009).On the virus side,attachment is mediated by the VP8*subunit of VP4:a shallow groove of the VP8*surface inter-acts with SAs on cellular glycans(Dormitzer et al.,2002a,2002b). More recently it has been demonstrated that certain RV strains,e.g. G10P[11],bind to non-SA containing histo blood group antigens (HBGA)via the Gal?1–4GlcNAc motif(Hu et al.,2012;Huang et al., 2012;Ramani et al.,2013).For the P[8]genotype it has been shown that its interaction with HBGA receptor depends on a functioning FUT2enzyme(Imbert-Marcille et al.,2014).Interestingly,certain RVs and noroviruses both use polymorphic HBGA receptors for attachment(Tan and Jiang,2014;Le Pendu et al.,2014).Various cel-lular surface molecules can act as(post-attachment)co-receptors,
U.Desselberger/Virus Research190(2014)75–9679 Table2
Gene-protein assignments,protein localization and protein-function assignment adapted to bovine rotavirus RF strain(G6P6[1]).
Genome segment Size(bp)Encoded protein Size(kDa)Location in virion Molecules/virion Functions
13302VP1125Core12RdRp;ssRNA binding;complex with VP3
22687VP294Core120Core shell;RNA binding;required for RdRp activity 32592VP388Core12Guanylyltransferase;methyltransferase;
2 ,5 -phosphodiesterase;ssRNA binding;complex with
VP1
42362VP4a86Outer layer180Homotrimer;P type neutralization antigen;
attachment protein;protease enhanced infectivity;
virulence;fusion with cell membrane 51581NSP158Nonstructural Interferon antagonist;E3ligase;RNA binding 61356VP644Middle layer780Homotrimer,species determinant;protection
(intracellular neutralization);required for
transcription
71062VP7b37Outer layer780Homotrimer;glycoprotein;G type neutralization
antigen;Ca2+dependent 81059NSP236Nonstructural Octamer;binds RNA,NTPase;NDP kinase;helix
destabilizing;essential for viroplasm formation 91074NSP334Nonstructural Dimer;binds to:3 terminus of viral ss(+)RNA,cellular
eIF4G,Hsp90;displaces PABP;inhibits host protein
translation
10751NSP420Mainly nonstructural Very few RER transmembrane glycoprotein;viroporin;
intracellular receptor for DLPs;interacts with
viroplasms and autophagy pathway;modulates
intracellular Ca2+and RNA replication;enterotoxin
(secreted);virulence
11666NSP521Nonstructural Dimer;phospho-and O-glycosylated protein;RNA
binding;kinase;essential for viroplasm formation;
interaction with VP2
NSP6c12Nonstructural Interaction with NSP5,localized in viroplasm
a Cleaved by trypsin or cellular protease into VP5*+VP8*.
b Signal peptide cleaved off.
c Secon
d ORF of RNA11.
such as several integrins(?2?1,???3,?x?2,?4?1),which react with integrin ligand motifs on VP5*or VP7(motif DGE on VP5*or motifs GPR and CNP on VP7)(Coulson et al.,1997;Graham et al., 2003;Zárate et al.,2004;Gutiérrez et al.,2010),or with the human heat shock cognate protein70(Hsc70)(Guerrero et al.,2002;Zárate et al.,2003;Pérez-Vargas et al.,2006).All co-receptors are asso-ciated with lipid rafts,i.e.detergent-resistant lipids close to the cellular plasma membrane acting as platforms on which RV TLPs associate(Isa et al.,2004).The relative importance of the vari-ous receptors for human RV infection is beginning to be assessed (Fleming et al.,2014).
It should be noted that some RV strains hemagglutinate(Kalica et al.,1978;Bastardo and Holmes,1980)and that it is the VP8* component of VP4(at the tip of the spikes)which mediates this interaction(Mackow et al.,1989;Fiore et al.,1991).
5.2.Virus particle penetration and uncoating
Before trypsin cleavage,VP4spikes are?exible and thus not vis-ible by EM,although they are present in a virtually identical struc-ture as recently con?rmed by single particle cryo-ET(Rodríguez et al.,2014).Upon contact with the cellular receptor,the VP4spikes of RV TLPs undergo conformational changes in such a way that the lipophilic domains of VP5*which are normally hidden below VP8* are exposed on the surface in form of a‘post-penetration umbrella’conformation(Kim et al.,2010;Trask et al.,2010a;Settembre et al., 2011).Treatment of RV particles with trypsin seems to favor this transition(Crawford et al.,2001;Rodríguez et al.,2014)and convey full infectivity to the TLPs(Estes et al.,1981).Partially trypsin-resistant RV mutants were shown to have a delay in cellular entry, but then to replicate as well as wildtype(wt)virus(Trask et al., 2013).Following binding,the mechanism of cell penetration of RV particles remains unclear;it may occur by receptor-mediated endo-cytosis or direct membrane penetration,with solubilization of the outer capsid proteins due to low Ca2+concentrations in endosomes (Ludert et al.,1987)to yield DLPs.The presence of cholesterol and of the GTPase dynamin on cell membranes are required for RV entry, but not for all RV strains(Sánchez-San Martín et al.,2004).Genome-wide RNAi screening revealed that components of the‘endosomal sorting complex for transport’(ESCRT)are involved in RV entry (Silva-Ayala et al.,2013).RV strains differ in the usage of endo-somal pathways;some require Rab7-mediated transport to late endosomes(Díaz-Salinas et al.,2014).
5.3.RV plus strand(m)RNA synthesis
RV particles possess their own transcription complexes(TCs), consisting of VP1,the viral RNA-dependent RNA polymerase (RdRp),and VP3,the viral capping enzyme(with phosphodieste-rase,guanylyltransferase and methylase activities).The TCs are localized at the inner surface of the VP2(core)layer at the?ve-fold symmetry axes,i.e.at11or12vertices(Jayaram et al.,2004). Each TC is complexed with a dedicated viral RNA segment(Periz et al.,2013).Rotavirus DLPs in cytoplasm produce capped,non-polyadenylated,(+)ssRNA transcripts(from the negative strand of the genomic RNA)which are released from the particle through the class I channels(Fig.1E and F).The transcripts serve either for trans-lation of virus-encoded proteins(early in the replication cycle)or as templates for replication(late in the replication cycle)to become the dsRNA genomes of RV progeny(Silvestri et al.,2004).Parti-cles of the Reoviridae family can produce mRNAs of a maximum of12different genomic segments(e.g.in the genus Coltivirus).For the Rotavirus(11genomic RNA segments)and Orthoreovirus(10 genomic RNA segments)genera it is not clear whether the1–2‘extra’TCs are occupied by RNAs or are‘empty’.RV DLPs are‘tran-scriptionally active’in the cellular cytoplasm and in vitro,where they produce large amounts(in mg range)of mRNAs,provided pre-cursors and an energy source(ATP)are in suf?cient supply(Cohen et al.,1979;Spencer and Arias,1981;Lawton et al.,1997;Lu et al., 2008).A logarithmic increase in mRNA production at later stages
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Fig.4.The rotavirus replication cycle.The rotavirus triple layered particles (TLPs)?rst attach to sialo-glycans (or histo-blood group antigens)on the host cell surface,followed by interactions with other cellular receptors,including integrins and Hsc70.Virus is then internalized by receptor-mediated endocytosis.Removal of the outer layer,triggered by the low calcium of the endosome,results in the release of transcriptionally active double-layered particles (DLPs)into the cytoplasm.The DLPs start rounds of mRNA transcription,and these mRNAs are used to translate viral proteins.Once enough viral proteins are made,the RNA genome is replicated and packaged into newly made DLPs in specialized structures called viroplasms,which interact with lipid droplets.The newly made DLPs bind to NSP4,which serves as an endoplasmic reticulum (ER)receptor,and bud into the ER.NSP4also acts as a viroporin to release Ca 2+from intracellular stores.Transiently enveloped particles are seen in the ER.The transient membranes are removed as the outer capsid proteins VP4and VP7assemble,resulting in the maturation of the TLPs.The progeny virions are released through cell lysis.In polarized epithelial cells,particles are released by a non-classical vesicular transport mechanism.For further details see text.
From Estes and Greenberg (2013).With permission of the authors and the publisher.
of infection (>4h p.i.)indicates that the newly synthesized DLPs have become transcription active (secondary transcription)(Stacy-Phipps and Patton,1987;Ayala-Breton et al.,2009).Rotavirus segment-speci?c mRNAs extruded from DLPs are then translated into the encoded proteins in the cytoplasm (see above and Table 2).
5.4.Viroplasm formation
Rotavirus proteins and RNAs interact speci?cally in cytoplasmic inclusion bodies termed ‘viroplasms’.In order for viroplasms to form,the presence of two of the RV non-structural proteins,NSP2and NSP5,is essential and suf?cient,since co-expression of NSP2and NSP5in uninfected cells leads to the production of viroplasm-like structures (Fabbretti et al.,1999).Blockage of these two proteins by speci?c siRNAs,intrabodies or the use of NSP2-or NSP5-speci?c RV ts mutants at the non-permissive temperature prevent viroplasm formation,RV morphogenesis and the pro-duction of infectious RV progeny (Silvestri et al.,2004;Vascotto et al.,2004;Campagna et al.,2005).Recently,the conversion of ‘cytoplasmic into ‘viroplasm-associated by interaction with hypophosphorylated NSP5has been observed,which is followed
by phosphorylation of both molecules (Criglar et al.,2014).Cyto-plasmic NSP2also forms complexes with VP1,VP2and tubulin (Criglar et al.,2014),making tubulin a component of viroplasms (Martin et al.,2010),and induces microtubule depolymerization and stabilization by acetylation (Martin et al.,2010;Eichwald et al.,2012).Functional proteasomes and components of the autophagic pathway are essential for viroplasm formation and RV replication (Contin et al.,2011;López et al.,2011;Arnoldi et al.,2014).NSP2forms octamers and has nucleoside triphosphatase,RNA helix destabilizing and nucleoside diphosphate kinase activities (Taraporewala et al.,1999;Taraporewala and Patton,2001,2004;Jiang et al.,2006).Grooves in the NSP2octamer are binding sites for which NSP5and ssRNAs compete,thus possibly regulating the balance between RV RNA translation and replication (Jiang et al.,2006).NSP5is a serine-and threonine-rich protein which occurs in oligomeric forms and becomes hyperphosphorylated (Torres-Vega et al.,2000;Eichwald et al.,2004;Criglar et al.,2014).The exact biochemical functions of NSP5remain to be determined (Campagna et al.,2007;Contin et al.,2010;Criglar et al.,2014).
NSP4,a transmembrane glycoprotein,is mainly located in the endoplasmic reticulum (ER)and has multiple functions:(1)It
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serves as an intracellular receptor for DLPs by interacting with VP6 (Taylor et al.,1996).(2)It releases Ca2+from intracellular stores (Tian et al.,1994)by acting as a viroporin(Hyser et al.,2010, 2012),thus elevating the intracellular Ca2+levels needed to sta-bilize the outer layer of TLPs.The viroporin function was found to be due to interaction of NSP4with the cellular Ca2+sensor molecule STIM1(Hyser et al.,2013).(3)NSP4forms caps on viro-plasms and co-localizes with the autophagy protein LC3(Berkova et al.,2006).The NSP4-triggered increase of intracellular(Ca2+) activates a kinase-dependent pathway,which leads to autophagy (Crawford et al.,2012;Crawford and Estes,2013).(4)NSP4alters plasma membrane permeability(Newton et al.,1997)and destabi-lizes intercellular junctions(Tian et al.,1996).(5)Most importantly, NSP4was discovered to act as a viral enterotoxin(Ball et al.,1996): it is secreted early after RV infection,either as a peptide fragment or as a whole molecule(Zhang et al.,2000;Bugarcic and Taylor,2006) and interacts with non-infected intestinal cells by integrin?1?1 and?2?1receptors located at their basolateral plasma membranes (Seo et al.,2008).The activated integrin receptors stimulate intra-cellular reaction cascades which are correlated with intracellular Ca2+release and diarrhea.NSP4exists in3pools in the infected cell (Berkova et al.,2006):(1)localized in the ER as receptor for DLPs;
(2)being secreted by the cell as a soluble component(Zhang et al., 2000;Bugarcic and Taylor,2006);(3)forming‘caps’on viroplasms (Berkova et al.,2006).
The RV NSP3protein has been found to interact(at its N termi-nus)with the3 terminus of viral(+)ssRNA and(at its C terminus) with the translation factor eIF4G(bound to the5 terminus of the RNA),thus circularizing the viral RNA and functioning like the polyA binding protein(PABP)for cellular mRNAs(Piron et al., 1998,1999;Vende et al.,2000;Groft and Burley,2002).Since NSP3can evict the PABP from cellular mRNAs,it prevents cellu-lar mRNA translation very ef?ciently(Piron et al.,1998;Groft and Burley,2002).Inhibition of NSP3expression by siRNA,however, mainly suppresses its effect on cellular mRNA translation;viral RNA translation is not impaired(Montero et al.,2006).Cellular mRNA translation is inhibited by expressed NSP3leading to the accumu-lation of PABP and of the cellular mRNAs themselves in the cell nucleus(Montero et al.,2006;Harb et al.,2008;Rubio et al.,2013). NSP3also antagonizes part of the innate immune response(see below).
NSP1is the most variable of all RV proteins.It is likely involved in host range restriction(Broome et al.,1993;Feng et al.,2013).
A key function of NSP1is its ability to act as an antagonist of the innate immune response(see below).
Viroplasms recruit cellular lipid droplets(LDs)which serve as energy store and transport vehicles in the cell(Cheung et al.,2010; Crawford et al.,2013).Analysis of the lipidome of viroplasm-LD complexes has con?rmed their interaction(Gaunt et al.,2013b). Interference with LD homoeostasis and blockage of neutral fat breakdown decrease the number and size of viroplasms and the production and infectivity of viral progeny(Cheung et al.,2010; Crawford et al.,2013;Gaunt et al.,2013a).
5.5.RNA packaging,minus strand RNA synthesis and DLP
formation
Due to their persistence length of1130?A(Kapahnke et al.,1986), naked dsRNAs cannot be packaged into core shells.Rather,the11 different(+)ssRNA segments are reassorted,interact with viral core proteins(see above)and are then packaged and replicated.It is assumed(Trask et al.,2012a)that primary replication complexes of VP1/VP3/ssRNA interact with a VP2decamer(most likely involv-ing NSP5and NSP2)(Berois et al.,2003),leading to the formation of core particles.During this process,the negative charge of the RNA has to be neutralized by co-packaging of either divalent cations or spermidine,a cellular trivalent cationic compound(Gouet et al., 1999;Desselberger et al.,2013).The N-terminal domain of VP2is essential for the encapsidation of VP1(and the attached ssRNA) (Zeng et al.,1998;Boudreaux et al.,2013).Complex formation with VP2is essential for the RdRp activity of VP1,with VP1/VP2com-plexes constituting the minimal replicase particles in vitro(Zeng et al.,1996).The molecular details of the early morphogenesis of RV particles(core particle formation and RNA replication)are not well understood.In particular,it is unclear how the packaging of the correct set of11RNA segments into individual particles is con-trolled.Once formed,core particles are rapidly transcapsidated by VP6,leading to the synthesis of DLPs.The latter process has been studied in vitro(Trask and Dormitzer,2006;Desselberger et al., 2013).
5.6.Virus particle(virion)maturation and release
RV DLPs,upon leaving the viroplasms,bud through the endo-plasmic reticulum(ER)for maturation.In this process,NSP4 serves as an intercellular receptor by interacting with VP6(Taylor et al.,1996).Within the ER,nascent RV particles are transiently enveloped,but the envelope is lost when RV particles acquire the outer layer consisting of VP4(60trimers)and VP7(260trimers). (Estes and Greenberg,2013).The origin,function and loss of the transitory envelope are not understood.However,it is likely that VP4trimers,which form spikes,react with VP6?rst and are then embedded in a continuous layer of VP7trimers(Trask and Dormitzer,2006)(Fig.3).Transcapsidation experiments in vitro have shown that only by VP4interacting with DLPs?rst,followed by interaction with VP7,full infectivity of TLPs can be restored (Trask and Dormitzer,2006).Another pool of VP4interacts with the cellular plasma membrane(González et al.,2000;Nejmeddine et al.,2000;Delmas et al.,2007).As described above,by interacting with DLPs NSP4has a crucial function in the maturation process: blockage of NSP4expression by siRNA leads to RV particle matura-tion defects(Silvestri et al.,2005),and RV RNA replication is also inhibited,possibly by the NSP4fraction interacting with viroplasms (Berkova et al.,2006).RV TLPs are released from non-polarized cells (MA104)by lysis(McNulty et al.,1976),but from epithelial cells(e.g. Caco-2)by a kind of budding process that does not immediately kill the cell(Gardet et al.,2006).
5.7.Persistent RV infection
In cell culture and in immunocompromised hosts(humans and other mammalian species)RV infection can become persistent (Estes and Graham,1980;Chiarini et al.,1983;Riepenhoff-Talty et al.,1987;Mrukowicz et al.,1998).The detailed molecular mech-anisms of this virus–host relationship are poorly understood at present.
5.8.Growth of RVs in stem cell organoids
Following the achievement of differentiating human stem cell lines in vitro into intestinal cell-like cultures(human intestinal organoids)(Spence et al.,2011),it was shown that such cultures can be infected with RVs,both laboratory strains(SA11)and clinical isolates(Finkbeiner et al.,2012).The full potential of such cultures for studying RV replication is in the process of being explored.
5.9.Cellular proteins involved in RV replication
As obligate cellular parasites viruses require cellular functions for their replication.Most viruses do not possess the machinery to translate proteins from their mRNAs and rely on the translation organelles and functions of the host cell.More recently,a much
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wider involvement of cellular compounds and functions in virus replication was uncovered.For RVs those are:
-cellular receptors and co-receptors for adsorption(section V.1), -cellular endosomes for uncoating of TLPs to DLPs(section V.2), -interaction of the‘viral factory’viroplasms with LDs(Section5.4), -interaction of NSP3with components of the cellular translation machinery,
-interaction of NSP4with cellular membranes containing the intracellular Ca2+stores(Section5.4),
-interaction of viral NS proteins with cellular structural proteins (actin,micro?laments),
-interaction of NSP1with various components of the cellular innate immune response(see below).
6.RV genetics and reverse genetics
RV functions have been explored by genetic studies with sponta-neous mutants,but mainly by determining reassortment groups of ts mutant collections at the non-permissive temperature.Thus,for SA11RV,10out of the11expected reassortment groups have been identi?ed,and9of them assigned to individual genome segments (Criglar et al.,2011;Vende et al.,2013).
Several reverse genetics(RG)systems for RVs have been described,but so far they all depend on the presence of a helper virus and require strong selection conditions.Thus,VP4genes (native or chimeric)transcribed from a cDNA plasmid have been rescued into viable virus in the presence of neutralizing antibody directed against the VP4of the helper virus(Komoto et al.,2006, 2011).A dual selection mechanism(use of ts mutants of the helper virus at the non-permissive temperature,and of siRNA directed against the helper virus gene of interest for engineered reassort-ment)has been applied to drive single gene RG(Trask et al.,2010b) (Fig.5).Using this technique,it has been possible to engineer par-tial gene duplications and heterologous cDNA sequences(encoding FLAG,a hepatitis C virus E2epitope and an IRES sequence)into the 3 UTR of the NSP2gene of the SA11RV(Navarro et al.,2013),thus opening the potential of creating a recombinant RV that can act as a viral vector.In addition,rearranged genome segments transcribed from cDNA were engineered into helper virus,possibly based on the preferential packaging of rearranged genes(Troupin et al.,2010).
Attempts to establish a helper virus-free,fully tractable and uni-versally applicable RG system for RV have so far failed,in contrast to successful,RNA-or plasmid-only based RG systems for orthore-ovirus(Kobayashi et al.,2007)and orbivirus(Boyce et al.,2008). Following the lead of Boyce et al.(Boyce et al.,2008),who res-cued infectious bluetongue virus after co-transfection of the10 full-length(+)ssRNA transcripts,Richards et al.(Richards et al., 2013)were unable to rescue viable RVs.The main impediment seemed to be a lack of translation of transfected full-length RV RNAs or cDNAs(with the RV insert downstream from a T7pro-moter,in the presence of a fowlpox virus-T7recombinant)and a strong cytotoxic effect of transfected RNAs.O’Neill et al.(2013), Wentzel et al.(2013)and Wentzel(2014)observed translation of several transfected full-length RNA segments,possibly by using different cell lines,but also recorded a high degree of cytotox-icity which they considered to be caused by an extremely high stimulation of the innate immune response.Despite progress in obtaining translation of transfected RV RNAs,this research group could not rescue infectious RV progeny from RNA co-transfections alone,either.Taken together,work on plasmid-only or transcript-only based RG systems for RVs has so far only succeeded in helping to identify procedural bottlenecks which have to be overcome.
Despite the lack of a nucleic acid-only based RG system,it has been possible to incorporate in vivo-biotinylated VP6into infectious RV particles(De Lorenzo et al.,2012);the procedure should be useful for labelling and functional exploration of other RV structural proteins.
7.Molecular pathogenesis and pathophysiology
RVs mainly infect mature enterocytes at the top of the villi of the small intestine of mammalian species,where vacuolization and epithelial loss can be observed,followed by crypt hyperpla-sia.Although extraintestinal spread of RV occurs frequently as evidenced by detection of RV dsRNA,RV antigen,and(occasionally) infectious RV in serum and other host body sites(Blutt et al.,2003; Blutt and Conner,2007),the signi?cance of these observations for pathologic?ndings in normal(immunocompetent)hosts is con-troversial(Fenaux et al.,2006;Ramig,2007;Ramani et al.,2010). By contrast,in the immunocompromised hosts,RV can replicate in the liver,the biliary system and the pancreas and be associated with biliary atresia and pancreatitis(Gilger et al.,1992;Feng et al., 2008).A striking?nding(in animal models)is the onset of diarrhea at an early time point when histopathological changes of the small intestine are absent(Ward et al.,1996),likely due to early action of NSP4(Estes and Morris,1999;Estes and Greenberg,2013)which forms oligomers of different size(Bowman et al.,2000;Chacko et al., 2011).The pathogenesis of RV disease is multifactorial,depending on the age of host,homology/heterology of virus-host interaction, and particular viral gene products(VP3,VP4,VP7,NSP2,NSP3, NSP4;Broome et al.,1993;Ball et al.,1996;Burke and Desselberger, 1996;Estes and Atmar,2003;Ramig,2004;Greenberg and Estes, 2009).Using simian(RRV)-mouse(EW)RV reassortants,Feng et al. (2013)concluded that the genes encoding the mouse VP4and NSP1 were determinants for ef?cient replication in suckling mice.
Factors of the disease mechanism are:maladsorption following destruction of epithelium(Estes and Atmar,2003),villus ischemia (Osborne et al.,1991),the action of NSP4,a viral enterotoxin(Ball et al.,1996;Greenberg and Estes,2009;Chattopadhyay et al., 2013),and activation of the enteric nervous system(Lundgren et al.,2000).Recently,the pathogenesis of the symptom vomiting has also been elucidated by observations that RV can infect the enterochromaf?ne cells in the gut and stimulate the production of5-hydroxytryptamin(serotonin)which in turn activates vagal afferent nerves and stimulates brain stem structures controlling vomiting(Hagbom et al.,2011,2012).
Biliary atresia(BA)can be induced in newborn mice by RV infec-tion,leading to obstructive cholangiopathy,the severity of which depends on the host’s age at the time of infection and also on the presence and potency of innate immune responses(Mohanty et al., 2013).In this model,newborn mice can be protected from BA by passive immunization,achieved either by immunizing the dams with RV-like particles or by injecting hyperimmune serum into pubs prior to infection(Hertel et al.,2013).
A relatively novel area of the exploration of gut diseases is the metagenomic analysis of viruses and other microbes found in the gut(Finkbeiner et al.,2008;Minot et al.,2012,2013)and the corre-lation of their presence with https://www.360docs.net/doc/c88711488.html,ing this approach,genomes of viruses can be discovered the particles of which have not been previously observed nor isolated by cell culture.So far,mainly DNA viruses,many of them bacteriophages,were analyzed.Protocols to discover both DNA and RNA viruses in fecal specimens have been developed(Sachsenroder et al.,2012),and applications to the anal-ysis of the full human gut virome have started(Kapusinszky et al., 2012;Phan et al.,2012;Ryan,2013).It will be important to know whether and to what extent the human gut microbiome,including the virome,may in?uence the pathogenesis of chronic gut diseases (such as Crohn’s disease and colitis ulcerosa)(Virgin,2014).Using the gnotobiotic piglet model of human RV infection and disease,it
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83
Fig.5.Reverse genetics of a gene8recombinant rotavirus using a dual selection system.(A)Diagram of the recombinant gene8cDNA.A minimal T7RNA polymerase promoter(T7P)initiates transcription of an SA11gene8(+)RNA with an authentic5 end.The g8D RNAi target site was engineered to prevent targeting of the recombinant mRNA.Cleavage by a modi?ed HDV ribozyme(Rbzm)generates the authentic3 end.(B)Diagram of the reverse genetics method.COS-7cells are infected with rDIs-T7pol (VV-T7)(i)and transfected with the recombinant gene8plasmid(pBS-SA11g8R)(ii)before infection with the tsE helper virus at30?C(iii).The recovered virus stock contains both tsE helper virus and the tsE/SA11g8R virus.Passage at39?C in MA104-g8D cells(iv)allows rapid isolation of the tsE/SA11g8R virus(v).
From Trask et al.(2010b).With permission of the authors and the publisher.
was observed that properly dosed probiotic lactic acid bacteria can enhance the Th1and Th2cytokine responses and partially prevent RV-induced injuries to the gut epithelium(Azevedo et al.,2012;Liu et al.,2013).
8.Immune responses
8.1.RV-speci?c humoral and cell-mediated immune responses
Upon RV infection,acquired immune responses are elicited, both from B cells producing antibodies directed against virus-speci?c proteins,and from T cells recognizing T cell-speci?c RV epitopes on the surface of infected cells in complexes with MHC classes I and II antigens.Many antibodies directed against VP7and VP4on the surface of RV particles are neutralizing(NAb)in vitro and protective in vivo,as demonstrated by passive transfer in mice and gnotobiotic piglets as animal models(Of?t,1994;Feng et al., 1997;Franco and Greenberg,1997;Yuan and Saif,2002;Jiang et al., 2002).Passive transfer of RV-speci?c CD8+T cells has also shown to be protective(Of?t,1994).Transplacentally acquired RV-speci?c antibodies likely protect newborns from infection(Ray et al.,2007) and interfere with immune responses to RV vaccination(Johansson et al.,2008;Appaiahgari et al.,2014).The availability of various knockout mutant mice has permitted researchers to dissect the rel-ative contributions of humoral and cellular immune responses to protection:while RV-speci?c T cells help eliminate RV after primary infection,it is the RV-primed memory B cells which provide more long-term protection(Franco et al.,2006).Humoral antibodies boosted after repeated infection are directed against both serotype-speci?c and cross-reactive epitopes on VP4and VP7molecules,thus also providing heterotypic protection(Franco et al.,2006).Plasma-cytoid dendritic cells were found to be necessary and suf?cient to induce B cell activation after RV infection in mice(in vivo)and in human cells(in vitro)(Deal et al.,2013).Human RV-speci?c CD4+T cells circulating in the blood express the intestinal homing recep-tor?4?7(Gonzalez et al.,2003;Weitkamp et al.,2005;Parra et al., 2014).However,protection from RV infection is not entirely corre-lated with the concentration of VP4-and VP7-speci?c NAbs.Upon natural infection by or vaccination with RV,infants and young chil-dren develop antibodies against other structural(VP6,VP2)and nonstructural(NSP4)proteins.VP6-speci?c antibodies do not neu-tralize in vitro,but were shown to be protective in vivo(Burns et al.,1996),when VP6-speci?c antibodies of the IgA class were applied.It was suggested and has recently been proven that VP6-speci?c IgA antibodies are taken up(‘transcytosed’)by epithelial gut cells through J protein receptors at the basolateral membrane and form complexes with new DLPs released from viroplasm,thus preventing their maturation to TLPs(‘intracellular neutralization’) (Desselberger,1998;Schwartz-Cornil et al.,2002;Feng et al.,2002; Corthésy et al.,2006;Aiyegbo et al.,2013;Sapparapu et al.,2013). However,it has also been shown that mice and patients who are IgA-de?cient eliminate RV after infection,probably due to a com-pensatory IgG protective immunity(O’Neal et al.,2000).Passive transfer of NSP4antibody has produced some protection in mice (Hou et al.,2008),but actively acquired NSP4antibody does not protect gnotobiotic piglets from a challenge with RVA(Yuan et al., 2004).Prospective studies have shown that,after1or2natu-ral RV infections,children appear to be highly protected against severe disease following infection by various,also heterotypic,RVs (Velázquez et al.,1996).
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Fig.6.Modulation of the host innate immune system by RV infection.After entry into cells,actively transcribing RV is recognized by receptors RIG-I and MDA-5 which activate the transcription factors IRF3and NF-kB;in turn those migrate to the nucleus and stimulate interferon(IFN)and IFN stimulatory genes(ISG).The viral NSP1interacts with IRF3and other cellular proteins(NF-?B a.o.),which are then degraded.Interferon is secreted and,by binding to IFN receptors,activates transcription factors STAT-1,STAT-2,and IRF9which in turn further stimulate IFN production and establish an‘antiviral state’.For further details see text.
From Angel et al.(2012).With permission of the authors and the publisher.
8.2.Innate immune responses
RV infection immediately triggers various mechanisms of innate immune responses(IIR),which occur earlier than acquired RV-speci?c immune responses,at least after primary infection(Angel et al.,2012)(Fig.6).Many IIRs appear to be RV strain-speci?c and also cell type-speci?c(Feng et al.,2009).At present it is not fully clear to what extent the IIRs after RV infection modify dis-ease.It has been shown that the RV NSP1is able to interact with the following cellular proteins:interferon(IFN)regulatory factors (IRF)3(Graff et al.,2002,2007;Barro and Patton,2005;Sen et al., 2011),?-transducin repeat containing protein(?-TrCP0)(Graff et al.,2009;Qin et al.,2011),melanoma differentiation-associated gene5(MDA5)/mitochondrial antiviral signaling protein(MAVS) (Broquet et al.,2011;Sen et al.,2011;Nandi et al.,2014),the tumor suppressor protein p53(Bhowmick et al.,2013)and the TNF recep-tor associated factor2(TRAF2)(Bagchi et al.,2013),leading to their proteasomal degradation and thus preventing or down-regulating the early triggering of an IFN response.RV NSP1also induces down-regulation of IRF5and IRF7(Barro and Patton,2007)and targets retinoic acid-inducible gene I(RIG-I)(Broquet et al.,2011)which, however,is downregulated by a proteasome-independent pathway (Qin et al.,2011).NSP1interacts with IRF3by binding to the dimeri-sation domain of the protein(Arnold et al.,2013a,2013b).Rotavirus infection also inhibits STAT1phosphorylation and STAT1/STAT2 translocation to the nucleus and thereby the establishment of an IFN-induced‘antiviral state’(Holloway et al.,2009,2014;Holloway and Coulson,2013;Sen et al.,2014).In addition,the C-terminal domain of the RV capping enzyme,VP3,has recently been shown to contain a phosphodiesterase which cleaves2 ,5 -oligoadenylate, thereby preventing activation of RNase L and blocking a potent IIR host cell response(Zhang et al.,2013).RIG-I was found to act as a cytoplasmic sensor for ssRNAs extruded from transfected DLPs(Uzri and Greenberg,2013).NSP1targets the pro-apoptotic cellular protein p53,leading to its proteasomal degradation and thus delaying cell death during the early stages of RV replication (Bhowmick et al.,2013).
Combined?ow cytometry and single cell multiplex RT-PCR allowed the dissection of the IIRs of RV-infected and bystander intestinal epithelial cells in mice infected with a homologous RV; heterogeneity of induction and subversion of early IIRs was discov-ered(Sen et al.,2012).
Rotavirus infection causes more severe disease in mice de?cient in IFN signaling(Vancott et al.,2003;Feng et al.,2008,2011).Inter-feron production is a dominant IIR in RV-infected pigs(González et al.,2010)and humans(Wang et al.,2007).Human plasmacytoid dendritic cells do not replicate RV,but initiate a brisk IFN response that may stimulate B cell responses(Deal et al.,2013).
The virus-encoded nonstructural protein NSP4secreted from RV-infected cells was shown to induce the synthesis of pro-in?ammatory cytokines from murine macrophages(Ge et al.,2013). Human RV-speci?c CD4+and CD8+T cells and B cells express the gut homing receptor?4?7(Rojas et al.,2003,2008).Thus,RV components interact by various mechanisms with molecules and pathways of the cellular IIR.
8.3.Correlates of protection
In general,there is a correlation between the presence of cer-tain levels of humoral RV-speci?c antibody and protection(e.g. RV-speci?c copro IgA of>1:80;RV-speci?c serum IgA of>1:200; RV-speci?c serum IgG of>1:800)(Matsui et al.,1989a,1989b;Of?t, 1994).The signi?cance of RV-speci?c serum IgA antibody levels as correlates of protection has been claimed(Blutt et al.,2012;Patel et al.,2013;Cheuvart et al.,2013;Blutt and Conner,2013),but this remains controversial(Angel et al.,2012).However,since there is a lack of correlation between relatively low Nab titers after natural RV infection or vaccination and high levels of protective immu-nity achieved,additional factors of importance for protection are likely(Desselberger and Huppertz,2011).Interestingly,both cur-rently licensed RV vaccines are highly ef?cacious and effective in countries of temperate climate(see below),although the correlates of protection are incompletely de?ned(Franco et al.,2006;Angel et al.,2007;Desselberger and Huppertz,2011).
9.Clinical symptoms and differential diagnosis,laboratory diagnosis and treatment
RV infections can remain asymptomatic(see below)or lead to acute gastroenteritis(AGE)with mild to severe diarrhea,vomiting and various degrees of dehydration.The body temperature is often, but only moderately,elevated.Vomiting precedes diarrhea and lasts for a shorter time period(3vs5days).A massive electrolyte imbalance leads to often severe dehydration.Death from RV dis-ease is mainly due to severe dehydration and cardiovascular failure. Whereas death from RV-associated disease is rare in developed and semi-developed countries,mainly due to the timely availability of rehydration measures,it is a frequent outcome in countries of sub-Saharan Africa and southeast Asia(Tate et al.,2012).Upon natural infection or(inadvertent)vaccination,children with severe com-bined immunode?ciency(SCID)can develop a chronic RV infection and disease(Desselberger,1996;Patel et al.,2010).In chroni-cally infected children,RVs with‘unusual’RNA migration patterns emerge,due to genome rearrangements(Desselberger,1996).
The diagnosis of RV infection is by electron microscopy or ELISA (Brandt et al.,1981),and more recently by RT-PCR(Gouvea et al., 1990;Gentsch et al.,1992;Gómara et al.,2000;Iturriza-Gómara et al.,2004).Of those procedures,ELISA is applied most frequently in the routine diagnostic laboratory(due to the ease of use and speed of obtaining a result).However,RT-PCR,which is highly sensitive and speci?c(Richardson et al.,1998)and also suitable
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for genotyping(Fischer and Gentsch,2004;Iturriza-Gómara et al., 2004),has become the‘gold standard’of diagnostic discovery. Due to continuous genomic drift by point mutations(see below) the primers used for genotyping have to be changed periodi-cally(Iturriza-Gómara et al.,2000,2004;Simmonds et al.,2008). For the differential diagnosis of disease causes,the main viruses to be considered are human caliciviruses(norovirus,sapovirus), astroviruses and(less frequently)enteric adenoviruses and Aichi virus.Many of those can be searched for by multiplex RT-PCR assay(e.g.,Liu et al.,2011).Other viruses infecting the gut and remaining mostly asymptomatic are different enteroviruses and,in the immunocompromised,picobirnaviruses,cytomegalovirus and HIV(Desselberger and Gray,2013).
In an internally controlled study,the genomes of G10P[11] RVs isolated from20asymptomatic and19symptomatic neonates in Vellore,India,in2003/2004,were determined by dideoxynu-cleotide(Sanger)and next generation sequencing and found to be virtually identical.Most importantly,no nt or amino acid(aa)dif-ferences were found which were correlated with asymptomatic or symptomatic infection(Libonati et al.,2014).It was concluded that other,poorly de?ned factors would determine the appearance of clinical symptoms.
The treatment consists mainly of rehydration(orally or intra-venously)(American Academy of Pediatrics,1996;Desselberger, 1999;Atia and Buchman,2009;Guarino et al.,2012).Various com-positions of oral rehydration salts(ORS)have been devised(CHOICE Study Group,2001;Atia and Buchman,2009),and rice-based solu-tions are also successfully applied(Pizarro et al.,1991).The use of loperamide,anticholinergic drugs and adsorbents is not recom-mended(American Academy of Pediatrics,1996).Racecadotril,an encephalinase inhibitor suppressing the enteric nervous system activated after RV infection(Lundgren et al.,2000;Salazar-Lindo et al.,2000),granisetron,a serotonin receptor antagonist,and vasoactive intestinal peptide antagonists(Kordasti et al.,2004) were also found to be bene?cial in decreasing the severity of acute diarrhea.Oral solutions containing high concentrations of RV anti-body were found to be bene?cial therapeutically,as well as a preventative measure(Saulsbury et al.,1980;Ebina,1996).
Recently,llama-derived single-chain antibody fragments spe-ci?c for RV VP6were shown to be broadly cross-reactive in vitro and to decrease virus shedding in infected mice(van der Vaart et al., 2006;Garaicoechea et al.,2008;Aladin et al.,2012).This antibody was also ef?cacious in decreasing RV replication in gnotobiotic piglets(Vega et al.,2013)and had a moderately bene?cial effect on RV disease in humans(Sarker et al.,2013;Kang,2013;Tokuhara et al.,2013).The antibody fragment that is of only15kDa size (Joosten et al.,2003)remained active after long-term(>1year)stor-age and was resistant to heating at94?C for90min(Tokuhara et al., 2013).The llama antibody fragment was expressed at high levels in transgenic rice(MucoRice-ARP1);in pilot studies,it suppressed the RV load in both immunocompetent and immunode?cient mice and also conferred protection from RV infection(Tokuhara et al.,2013). This and similar antibody preparations have a realistic potential for therapeutic and prophylactic use in humans(Kang,2013).
Other therapeutic approaches consist of the use of the broad spectrum antiviral nitazoxanide(Rossignol et al.,2006;Teran et al., 2009;La Frazia et al.,2013)and–supported by work with gnoto-biotic piglets(Azevedo et al.,2012;Liu et al.,2013)–of probiotics (Fang et al.,2009;Grandy et al.,2010;Corrêa et al.,2011;Ciccarelli et al.,2013).
10.Molecular epidemiology and mechanisms of evolution
Rotaviruses cause5–10%of all cases of AGE in infants and young children of<5years of age,and30%of RV disease is severe enough to require treatment in primary care centers or hospitals(Malek et al., 2006;Parashar et al.,2006;Liu et al.,2012).In the US before vacci-nation,RVs caused3million disease episodes per annum,requiring 500,000visits to a medical doctor and60,000hospitalisations,but leading to only20–40deaths(Fischer et al.,2007;Esposito et al., 2011).Similar numbers were found to be valid in Europe,except that the number of deaths was about200(Soriano-Gabarróet al., 2006;Van Damme et al.,2007).In sub-Saharan African and in some south Asian countries,RV disease is associated with a high mortality (Parashar et al.,2009;Tate et al.,2012).
Despite the large genomic and antigenic diversity of RVs(see above),globally only a small number of RV types have prevailed in humans during the past3decades:RVs of types G1P1A[8], G2P1B[4],G3P1A[8],G4P1A[8],and more recently G9P1A[8]and G12P1A[8]have co-circulated at high frequency,contributing 80–90%of all RV infections in North America,Europe and Australia (Gentsch et al.,2005;Santos and Hoshino,2005;Iturriza-Gómara et al.,2011).By contrast,in African,Asian and South American countries,other genotypes such as G5,G6and G8are more preva-lent(Todd et al.,2010;Mwenda et al.,2010;da Silva et al.,2011; Kang et al.,2013;Luchs and Timenetsky,2014).Regarding the over-all prevalence estimates of particular RVA genotypes,the problem of sampling bias should not be underrated.
With the advent of RV genotyping by RT-PCR(Gouvea et al., 1990;Gentsch et al.,1992),detailed studies of the molecular epidemiology of RVs have become possible.Genotyping has an enormous value for assessing the evolution and epidemiological pathways of RVs in humans,mammals and birds(Matthijnssens et al.,2011b;Matthijnssens and Van Ranst,2012).However,the importance of RV typing for success of vaccination may have been overestimated.Among other facts,the broad heterotypic ef?cacy and effectiveness of a monovalent RV vaccine(Rotarix?)calls this ‘dogma’into question(see below).Outbreak of AGE caused by species B RVs have been observed in China(Hung et al.,1983,1984), and individual cases of species B RV infections have been detected in Bangladesh and India(Kelkar and Zade,2004;Lahon et al.,2013). RVC infections are mostly asymptomatic or clinically mild,but can cause diarrhea in adults(Nilsson et al.,2000).Infections with RVD, RVF and RVG are mainly discovered in birds.Infections with RVH were detected in piglets(Wakuda et al.,2011;Molinari et al.,2014; Marthaler et al.,2014)and in humans(Jiang et al.,2008b).
RVs are very contagious for the following reasons:(1)a low number of virus particles at a low ratio of(number of virus particles/infectious units)suf?ces to productively infect a sus-ceptible individual(Ward et al.,1986;Graham et al.,1987);(2) rotavirus particles are shed in large numbers in feces(up to1011 particles/ml)during the acute stage of the infection(Ward et al., 1984)or for longer periods by infected immunocompromised hosts(Patel et al.,2010);and(3)RV particles are very resistant to environmental conditions(temperature,pH,etc.;Estes et al., 1979;Keswick et al.,1983).The transmission is usually fecal–oral, the incubation period is short(1–2days).Attendance of day child care centers is a risk factor to acquire a symptomatic RV infection (Pickering et al.,1988;Dennehy et al.,2006).Small RV epidemics among the elderly(in old people’s homes,geriatric wards,etc.) have been observed(Hrdy,1987).Nosocomial RV infections are frequent and dif?cult to eliminate(Gleizes et al.,2006).
The evolution of RVs has been elucidated by widespread genome-wide RT-PCR genotyping supported by cDNA sequencing (Matthijnssens and Van Ranst,2012).Several mechanisms were identi?ed(Iturriza-Gomara et al.,2003):
-frequent point mutations in all RNA segments,either sporadically occurring or sequentially accumulating(Blackhall et al.,1996; Iturriza-Gómara et al.,2000;Arista et al.,2005;Simmonds et al.,
86U.Desselberger/Virus Research190(2014)75–96
2008;Martínez-Laso et al.,2009;Ianiro et al.,2013;Hemming and Vesikari,2013a,2013b;De Grazia et al.,2014);
-genome reassortment occurring in doubly infected individual cells and organisms in vivo(Iturriza-Gómara et al.,2001),often involved in zoonotic transmission(Steyer et al.,2008;Martella et al.,2010;Todd et al.,2010;Matthijnssens et al.,2011b;Papp et al.,2013;Mullick et al.,2013;Soma et al.,2013;Cowley et al., 2013;Luchs and Timenetsky,2014);
-genome rearrangements,consisting of partial duplications or deletions of nt sequences of individual segments,a special form of recombination(Pedley et al.,1984;Desselberger,1996;Kojima et al.,1996,2000);
-true genome recombination involving several segments(Parra et al.,2004;Phan et al.,2007;Cao et al.,2008;Martínez-Laso et al.,2009;Donker et al.,2011;Jere et al.,2011);
-several of the aforementioned mechanisms acting in combina-tion.
The main mechanisms appear to be point mutations that occur continuously due to the high error rate of the RV RdRp(Blackhall et al.,1996)and genome reassortments.Animal RVs can also be directly transmitted to humans(Soma et al.,2013;Steyer et al., 2013).
11.Prevention:development and universal application of
RV vaccines,issues arising from present RV vaccination programs
Since RVs were discovered as an important enteric pathogen in children more than40years ago,scientists and clinicians have joined forces to develop a rotavirus vaccine.From studies on animal models it had become evident that protection against RV disease can be achieved by passive transfer of RV-speci?c immune response products(antibodies,T cells)or by vaccination(Of?t et al., 1986a,1986b;Of?t,1994;Franco et al.,2006;Desselberger and Huppertz,2011).Prospective observations of young children have shown that:(1)primary RV infection occurred mostly during the ?rst year of life and was generally symptomatic;(2)reinfections with RVs during the?rst2–3years of life were frequent but rarely accompanied by AGE(even when infection occurred by RVs of G/P genotypes which differed from those of the original infection) (Velázquez et al.,1996);(3)the protection achieved after repeated natural infections was associated with the presence of RV anti-bodies in serum and,more importantly,in the gut(IgA antibodies) (Coulson et al.,1990,1992).Thus,RV disease in humans was?rmly recognized as being vaccine-preventable.Initially,live-attenuated vaccines were developed since they seemed optimal in mimicking a sequence of repeated natural infections with the result of pro-tection from severe disease(Jennerian approach)(Kapikian et al., 1996).Initial promising results with a live attenuated bovine RV vaccine(strain RIT4237)in Finland could not be reproduced by trials in developing countries,and work on this vaccine candidate was discontinued(Senturia et al.,1987).Another bovine RV,the WC3strain,and a simian RV,RRV,were similarly inef?cacious or of variable ef?cacy in their monovalent form(Bernstein et al.,1990; Georges-Courbot et al.,1991).A modi?ed Jennerian approach was used by developing a quadrivalent vaccine that consisted of a mixture of the attenuated RRV(G3P7[5])and of mono-reassortants containing the genes encoding VP7of the human G1,G2and G4 genotypes in the genetic background of the other10RNA segment of the RRV strain(Kapikian et al.,1996).The quadrivalent,RRV-based human reassortant vaccine was ef?cacious in several large phase III trials(Santosham et al.,1997;Pérez-Schael et al.,1997; Joensuu et al.,1997).Based on these results the vaccine was licensed and produced under the name of RotaShield?(Wyeth Lederle Vaccines)in1998.During1998/99it was applied as a universal mass vaccination(UMV)to more than1million children in the USA.However,when cases of gut intussusception(IS)occurred in temporal association with RV vaccination,postponement of the RV UMV was recommended by CDC and AAP(CDC,1999). In follow-up investigations,a vaccine-attributable risk of gut IS of approximately1:2500was estimated(Murphy et al.,2001), which led to the voluntary discontinuation of vaccine production by the manufacturer.A considerable controversy over the size of the vaccine-attributable risk of gut IS ensued(Peter and Myers, 2002;Murphy et al.,2003a,2003b;Haber et al.,2004;Glass et al., 2004;Bines,2005;Simonsen et al.,2005;Matson,2006),leading to a signi?cantly lower estimate(1:10,000or lower),questioning the wisdom of the recommendation to discontinue the use of the quadrivalent vaccine and raising the issue of the ethics of withholding the vaccine from developing countries in which mortality from RV disease is high(Weijer,2000).
Following this backlash,extensive efforts were made to develop alternative RV vaccines.One of them was a live-attenuated mono-valent(G1P1A[8])vaccine candidate,derived from the human RV isolate89–12and attenuated by serial passage in cell culture.In a large phase III clinical trial(Ruiz-Palacios et al.,2006),this vac-cine was found to be highly ef?cacious against severe RV disease caused by the homologous RV strain and also heterologous strains such as G3P[8],G4P[8],and also by G2P[4],although to a slightly lesser extent(Vesikari et al.,2007).The vaccine was licensed for universal vaccination of infants in2005,and since then in many countries throughout the world(produced as‘Rotarix?’by Glaxo-SmithKline,also termed RV1).Simultaneously,a pentavalent,live attenuated vaccine was developed,using the bovine RV WC3strain (G6P7[5])as a genetic backbone for5mono-reassortants which individually carried the genes encoding the human VP7types G1 to G4and the human VP4type P[8](produced as‘RotaTeq?’by Merck,also termed RV5).This vaccine also underwent a very suc-cessful phase III clinical trial(Vesikari et al.,2006)and was licensed from2006onwards in many countries throughout the world.
In post-marketing studies both vaccines were found to be highly effective(with protection rates of70to>90%)in developed countries(Patel and Parashar,2009;Boom et al.,2010;Vesikari et al.,2010a,2010b;Anderson et al.,2011;Buttery et al.,2011b; Giaquinto et al.,2011;Quintanar-Solares et al.,2011;Tate et al., 2011a,2011b,2013;Tregnaghi et al.,2011;Desai et al.,2012;Payne et al.,2013a;Cortese et al.,2013;Gasta?naduy et al.,2013;Rha et al., 2014;Leshem et al.,2014),signi?cantly decreasing RV-associated AGE necessitating visits to medical practitioners and hospitaliza-tion,and in some instances also decreasing mortality from the condition(Richardson et al.,2010;Gasta?naduy et al.,2013).There is no clear difference in ef?cacy between the two vaccines.As a sur-prising but welcome side effect,‘herd immunity’in non-vaccinated children was observed(Yi and Anderson,2013;Anderson et al., 2013;Dennehy,2013;Leshem et al.,2014).
There remains a very small vaccine-attributable risk for IS for both vaccines,at approximately1:50,000or less,which,however,is exceeded by the bene?ts of the vaccines(Buttery et al.,2011a;Patel et al.,2011;Greenberg,2011;Haber et al.,2013;Carlin et al.,2013; Parashar and Orenstein,2013;Glass and Parashar,2014;Weintraub et al.,2014;Yih et al.,2014).
In contrast to the high effectiveness of RV vaccination in devel-oped countries,in some middle and low income countries,such as Mexico,Nicaragua,Malawi,South Africa,Kenya,Mali,Bangladesh and Vietnam,the ef?cacy of the vaccine was found to be substan-tially(20–30%)lower(Armah et al.,2010;Madhi et al.,2010;Zaman et al.,2010)for reasons that are at present not fully understood (Lopman et al.,2012;Glass et al.,2014).One factor may be vita-min A de?ciency,as experimentally explored in gnotobiotic piglets (Vlasova et al.,2013;Chattha et al.,2013;Kandasamy et al.,2014).
U.Desselberger/Virus Research190(2014)75–9687
Since the mortality from RV-associated AGE is highest in the low income countries(Tate et al.,2012),WHO recommends since2009 that RV vaccination should be carried out in all countries,accepting the relatively lower vaccine effectiveness in low income countries (SAGE,2009;WHO,2013).
The?nding of porcine circovirus type1and2DNA,detected in the two licensed vaccines by metagenomic techniques,was ini-tially a shock,but then investigated and not found to be harmful for humans,and the use of the vaccines continues(Victoria et al.,2010; McClenahan et al.,2011;Dubin et al.,2013;Esona et al.,2014).
Although the monovalent RV1vaccine is highly effective against heterotypic G2P[4]RVs,the proportion of G2P[4]-associated AGE was higher in vaccinated than in unvaccinated hospitalized chil-dren(Matthijnssens et al.,2014).Others did not?nd a signi?cant, vaccine-attributable change in the prevalence of particular RV genotypes(Dennehy,2013;Hemming and Vesikari,2013a;Peláez-Carvajal et al.,2014;Donato et al.,2014).To obtain more clarity about this problem,the post-marketing surveillance of RV strains and genotype prevalence is continuing.
Since both RV vaccines contain live attenuated virus,it is not surprising that RV vaccine strain reassortants(between both RV vaccine strains and vaccine and wt strains which had arisen during natural co-circulation)were discovered(Bucardo et al.,2012;Boom et al.,2012;Hemming and Vesikari,2013b).
Another live attenuated RV,the human-bovine natural reas-sortant116E(G9P8[11],originally isolated from asymptomatically infected newborns in India),has been tested in a phase III clinical trial in India,and an ef?cacy against severe RV disease of56%was recorded(Bhandari et al.,2014)which is comparable with that of the R1and R5RV vaccines in middle and low income countries(see above).
Due to the high effectiveness of RV vaccine programs,the pre-dominant cause of hospitalization of children with AGE are now norovirus infections(Koo et al.,2013;Payne et al.,2013b;Hemming et al.,2013;Bucardo et al.,2014).
As alternatives to live attenuated vaccines,inactivated virus particles(Jiang et al.,2008a,2013;Wang et al.,2010),virus-like particles(VLPs)expressed from baculovirus recombinant-infected insect cells(Crawford et al.,1994;Conner et al.,1996;O’Neal et al.,1997;Ciarlet et al.,1998;Crawford et al.,1999;Azevedo et al.,2013)or yeast(Rodríguez-Limas et al.,2014),and DNA-based vaccines(Herrmann et al.,1996)are being explored.Rotavirus VP6nanotubules,also in combination with norovirus VLPs,are promoted as candidates for novel RV vaccines(Tamminen et al., 2013;Lappalainen et al.,2013;Rodríguez et al.,2013;Pastor et al., 2014).Experimentally,VP6-speci?c single chain antibodies(of only 15kDa MW)produced in llamas have been shown to have some cross-protective effect in vitro(Garaicoechea et al.,2008)and in vivo (Garaicoechea et al.,2008;Vega et al.,2013).
12.Perspectives of future basic and translational research
Major progress in basic RV research will depend on the estab-lishment of a tractable,helper virus-independent,plasmid(cDNA)-or RNA-only based reverse genetics system for RVs.
Based on the data reviewed,the following topics will require or are likely to attract research attention in the future:
-the3D structure of the dsRNA segments packaged in the RV core and their potential interaction with the core shell VP2;
-the different receptor speci?cities of different RV strains;
-details of the interaction of viroplasms with lipid droplets;
-the mechanisms controlling assortment/reassortment of11RNA segments in replication complexes(i.e.RNA/RNA interactions); -the mechanisms controlling RV RNA packaging;-the formation and loss of temporary enveloped RV particles in the ER during the viral maturation process;
-the potential of intestinal organoid cell cultures for the study of RV replication;
-the factors(mutations)determining RV pathogenicity and viru-lence;
-the molecular basis for host range and organ/cell speci?c viral replication;
-the signi?cance of the different arms of the immune response in establishing protection against RV disease;
-the full identi?cation of the correlates of protection against RV disease;
-the factors determining RV spread;
-the reasons for decreased ef?cacy of RV vaccines in reserve-strapped settings and areas of low socioeconomic conditions;
-the further evolution of human RVs under the condition of uni-versal mass vaccination against RV disease;
-the development of alternative(non-live attenuated)RV vaccine candidates;
-the development of RV antivirals.
Acknowledgements
The author’s work on rotaviruses has been made possible over the years by various grants,mainly from The Wellcome Trust and the MRC,both U.K.,and by institutional support from the CNRS,Gif-sur-Yvette,France(co-investigator:Dr J.Cohen), the ICGEB,Trieste,Italy(co-investigator:Dr O.Burrone)and the Department of Medicine,University of Cambridge,Cambridge,U.K. (co-investigator:Professor A Lever).The chapter on Rotaviruses by MK Estes and HB Greenberg in Fields Virology,6th edition,2013,has provided excellent guidance for this review.
References
Adams,W.R.,Kraft,L.M.,1963.Epizootic diarrhea of infant mice:identi?cation of the etiologic agent.Science141(July(3578)),359–360.
Aiyegbo,M.S.,Sapparapu,G.,Spiller,B.W.,Eli,I.M.,Williams,D.R.,Kim,R.,Lee,D.E., Liu,T.,Li,S.,Woods Jr.,V.L.,Nannemann,D.P.,Meiler,J.,Stewart,P.L.,Crowe Jr., J.E.,2013.Human rotavirus VP6-speci?c antibodies mediate intracellular neu-tralization by binding to a quaternary structure in the transcriptional pore.PLoS ONE8(May(5)),e61101.
Aladin,F.,Einerhand,A.W.,Bouma,J.,Bezemer,S.,Hermans,P.,Wolvers,D.,Bel-lamy,K.,Frenken,L.G.,Gray,J.,Iturriza-Gómara,M.,2012.In vitro neutralisation of rotavirus infection by two broadly speci?c recombinant monovalent llama-derived antibody fragments.PLoS ONE7(3),e32949.
American Academy of Pediatrics,1996.Practice parameter:the management of acute gastroenteritis in young children.Provisional Committee on Quality Improvement,Subcommittee on Acute Gastroenteritis.Pediatrics97,424–435. Anderson,E.J.,Rupp,A.,Shulman,S.T.,Wang,D.,Zheng,X.,Noskin,G.A.,2011.Impact of rotavirus vaccination on hospital-acquired rotavirus gastroenteritis in chil-dren.Pediatrics127(February(2)),e264–e270.
Anderson,E.J.,Shippee,D.B.,Weinrobe,M.H.,Davila,M.D.,Katz,B.Z.,Reddy,S.,Cuyu-gan,M.G.,Lee,S.Y.,Simons,Y.M.,Yogev,R.,Noskin,G.A.,2013.Indirect protection of adults from rotavirus by pediatric rotavirus vaccination.Clin.Infect.Dis.56 (March(6)),755–760.
Angel,J.,Franco,M.A.,Greenberg,H.B.,2007.Rotavirus vaccines:recent develop-ments and future considerations.Nat.Rev.Microbiol.5(July(7)),529–539. Angel,J.,Franco,M.A.,Greenberg,H.B.,2012.Rotavirus immune responses and cor-relates of protection.Curr.Opin.Virol.2(August(4)),419–425.
Appaiahgari,M.B.,Glass,R.,Singh,S.,Taneja,S.,Rongsen-Chandola,T.,Bhandari,N., Mishra,S.,Vrati,S.,2014.Transplacental rotavirus IgG interferes with immune response to live oral rotavirus vaccine ORV-116E in Indian infants.Vaccine32 (February(6)),651–656.
Arista,S.,Giammanco,G.M.,De Grazia,S.,Colomba,C.,Martella,V.,Cascio,A., Iturriza-Gòmara,M.,2005.G2rotavirus infections in an infantile population of the South of Italy:variability of viral strains over time.J.Med.Virol.77 (December(4)),587–594.
Armah,G.E.,Sow,S.O.,Breiman,R.F.,Dallas,M.J.,Tapia,M.D.,Feikin,D.R.,Binka,
F.N.,Steele,A.D.,Laserson,K.F.,Ansah,N.A.,Levine,M.M.,Lewis,K.,Coia,M.L.,
Attah-Poku,M.,Ojwando,J.,Rivers,S.B.,Victor,J.C.,Nyambane,G.,Hodgson,A., Sch?del,F.,Ciarlet,M.,Neuzil,K.M.,2010.Ef?cacy of pentavalent rotavirus vac-cine against severe rotavirus gastroenteritis in infants in developing countries in sub-Saharan Africa:a randomised,double-blind,placebo-controlled https://www.360docs.net/doc/c88711488.html,ncet 376(August(9741)),606–614.
88U.Desselberger/Virus Research190(2014)75–96
Arnold,M.M.,Barro,M.,Patton,J.T.,2013a.Rotavirus NSP1mediates degradation of interferon regulatory factors through targeting of the dimerization domain.J.
Virol.87(September(17)),9813–9821.
Arnold,M.M.,Sen,A.,Greenberg,H.B.,Patton,J.T.,2013b.The battle between rotavirus and its host for control of the interferon signaling pathway.PLoS Pathog.9(January(1)),e1003064.
Arnoldi,F.,De Lorenzo,G.,Mano,M.,Schraner,E.M.,Wild,P.,Eichwald,C.,2014.
Burrone OR Rotavirus increases levels of lipidated LC3supporting accumulation of infectious progeny virus without inducing autophagosome formation.PLoS ONE9(April(4)),e95197.
Atia,A.N.,Buchman,A.L.,2009.Oral rehydration solutions in non-cholera diarrhea:
a review.Am.J.Gastroenterol.104(October(10)),2596–2604.
Ayala-Breton,C.,Arias,M.,Espinosa,R.,Romero,P.,Arias,C.F.,López,S.,2009.Anal-ysis of the kinetics of transcription and replication of the rotavirus genome by RNA interference.J.Virol.83(September(17)),8819–8831.
Azevedo,M.P.,Vlasova,A.N.,Saif,L.J.,2013.Human rotavirus virus-like particle vac-cines evaluated in a neonatal gnotobiotic pig model of human rotavirus disease.
Expert Rev.Vaccines12(February(2)),169–181.
Azevedo,M.S.,Zhang,W.,Wen,K.,Gonzalez,A.M.,Saif,L.J.,Yousef,A.E.,Yuan,L., https://www.360docs.net/doc/c88711488.html,ctobacillus acidophilus and Lactobacillus reuteri modulate cytokine responses in gnotobiotic pigs infected with human rotavirus.Benef.Microbes3 (March(1)),33–42.
Bagchi,P.,Bhowmick,R.,Nandi,S.,Kant Nayak,M.,Chawla-Sarkar,M.,2013.
Rotavirus NSP1inhibits interferon induced non-canonical NF?B activation by interacting with TNF receptor associated factor2.Virology444(September (1–2)),41–44.
Ball,J.M.,Tian,P.,Zeng,C.Q.,Morris,A.P.,Estes,M.K.,1996.Age-dependent diarrhea induced by a rotaviral nonstructural glycoprotein.Science272(April(5258)), 101–104.
Barro,M.,Patton,J.T.,2005.Rotavirus nonstructural protein1subverts innate immune response by inducing degradation of IFN regulatory factor3.Proc.Natl.
Acad.Sci.U.S.A.102(March(11)),4114–4119.
Barro,M.,Patton,J.T.,2007.Rotavirus NSP1inhibits expression of type I interferon by antagonizing the function of interferon regulatory factors IRF3,IRF5,and IRF7.
J.Virol.81(May(9)),4473–4481.
Bastardo,J.W.,Holmes,I.H.,1980.Attachment of SA-11rotavirus to erythrocyte receptors.Infect.Immun.29(September(3)),1134–1140.
Berkova,Z.,Crawford,S.E.,Trugnan,G.,Yoshimori,T.,Morris,A.P.,Estes,M.K.,2006.
Rotavirus NSP4induces a novel vesicular compartment regulated by calcium and associated with viroplasms.J.Virol.80(June(12)),6061–6071. Bernstein,D.I.,Smith,V.E.,Sander,D.S.,Pax,K.A.,Schiff,G.M.,Ward,R.L.,1990.Eval-uation of WC3rotavirus vaccine and correlates of protection in healthy infants.
J.Infect.Dis.162(November(5)),1055–1062.
Berois,M.,Sapin,C.,Erk,I.,Poncet,D.,Cohen,J.,2003.Rotavirus nonstructural pro-tein NSP5interacts with major core protein VP2.J.Virol.77(February(3)), 1757–1763.
Bhandari,N.,Rongsen-Chandola,T.,Bavdekar,A.,John,J.,Antony,K.,Taneja,S.,Goyal, N.,Kawade,A.,Kang,G.,Rathore,S.S.,Juvekar,S.,Muliyil,J.,Arya,A.,Shaikh,H., Abraham,V.,Vrati,S.,Proschan,M.,Kohberger,R.,Thiry,G.,Glass,R.,Greenberg,
H.B.,Curlin,G.,Mohan,K.,Harshavardhan,G.V.,Prasad,S.,Rao,T.S.,Boslego,J.,
Bhan,M.K.,for the India Rotavirus Vaccine Group,2014.Ef?cacy of a monovalent human-bovine(116E)rotavirus vaccine in Indian infants:a randomised,double-blind,placebo-controlled https://www.360docs.net/doc/c88711488.html,ncet(March),pii:S0140-6736(13)62630-6. Bhowmick,R.,Halder,U.C.,Chattopadhyay,S.,Nayak,M.K.,Chawla-Sarkar,M., 2013.Rotavirus-encoded nonstructural protein1modulates cellular apoptotic machinery by targeting tumor suppressor protein p53.J.Virol.87(June(12)), 6840–6850.
Bines,J.E.,2005.Rotavirus vaccines and intussusception risk.Curr.Opin.Gastroen-terol.21(January(1)),20–25.
Bishop,R.F.,Davidson,G.P.,Holmes,I.H.,Ruck,B.J.,1973.Virus particles in epithelial cells of duodenal mucosa from children with acute non-bacterial gastroenteritis.
Lancet2(December(7841)),1281–1283.
Blackhall,J.,Fuentes,A.,Magnusson,G.,1996.Genetic stability of a porcine rotavirus RNA segment during repeated plaque isolation.Virology225(November(1)), 181–190.
Blutt,S.E.,Conner,M.E.,2007.Rotavirus:to the gut and beyond!Curr.Opin.Gas-troenterol.23(January(1)),39–43.
Blutt,S.E.,Conner,M.E.,2013.The gastrointestinal frontier:IgA and viruses.Front.
Immunol.4(November),402.
Blutt,S.E.,Miller,A.D.,Salmon,S.L.,Metzger,D.W.,Conner,M.E.,2012.IgA is impor-tant for clearance and critical for protection from rotavirus infection.Mucosal Immunol.5(November(6)),712–719.
Blutt,S.E.,Kirkwood,C.D.,Parre?no,V.,War?eld,K.L.,Ciarlet,M.,Estes,M.K.,Bok, K.,Bishop,R.F.,Conner,M.E.,2003.Rotavirus antigenaemia and viraemia:a common event?Lancet362(November(9394)),1445–1449.
Boom,J.A.,Sahni,L.C.,Payne,D.C.,Gautam,R.,Lyde,F.,Mijatovic-Rustempasic,S., Bowen,M.D.,Tate,J.E.,Rench,M.A.,Gentsch,J.R.,Parashar,U.D.,Baker,C.J., 2012.Symptomatic infection and detection of vaccine and vaccine-reassortant rotavirus strains in5children:a case series.J.Infect.Dis.206,1275–1279. Boom,J.A.,Tate,J.E.,Sahni,L.C.,Rench,M.A.,Quaye,O.,Mijatovic-Rustempasic,S., Patel,M.M.,Baker,C.J.,Parashar,U.D.,2010.Sustained protection from penta-valent rotavirus vaccination during the second year of life at a large,urban United States pediatric hospital.Pediatr.Infect.Dis.J.29(December(12)),1133–1135. Boudreaux,C.E.,Vile,D.C.,Gilmore,B.L.,Tanner,J.R.,Kelly,D.F.,McDonald,S.M., 2013.Rotavirus core shell subdomains involved in polymerase encapsidation into virus-like particles.J.Gen.Virol.94(August(Pt8)),1818–1826.Bowman,G.D.,Nodelman,I.M.,Levy,O.,Lin,S.L.,Tian,P.,Zamb,T.J.,Udem,S.A., Venkataraghavan,B.,Schutt,C.E.,2000.Crystal structure of the oligomerization domain of NSP4from rotavirus reveals a core metal-binding site.J.Mol.Biol.
304(December(5)),861–871.
Boyce,M.,Celma,C.C.,Roy,P.,2008.Development of reverse genetics systems for bluetongue virus:recovery of infectious virus from synthetic RNA transcripts.J.
Virol.82(September(17)),8339–8348.
Brandt,C.D.,Kim,H.W.,Rodriguez,W.J.,Thomas,L.,Yolken,R.H.,Arrobio,J.O., Kapikian,A.Z.,Parrott,R.H.,Chanock,R.M.,https://www.360docs.net/doc/c88711488.html,parison of direct elec-tron microscopy,immune electron microscopy,and rotavirus enzyme-linked immunosorbent assay for detection of gastroenteritis viruses in children.J.Clin.
Microbiol.13(May(5)),976–981.
Broome,R.L.,Vo,P.T.,Ward,R.L.,Clark,H.F.,Greenberg,H.B.,1993.Murine rotavirus genes encoding outer capsid proteins VP4and VP7are not major determinants of host range restriction and virulence.J.Virol.67(May(5)),2448–2455. Broquet,A.H.,Hirata,Y.,McAllister,C.S.,Kagnoff,M.F.,2011.RIG-I/MDA5/MAVS are required to signal a protective IFN response in rotavirus-infected intestinal epithelium.J.Immunol.186(February(3)),1618–1626.
Bucardo,F.,Reyes,Y.,Svensson,L.,Nordgren,J.,2014.Predominance of norovirus and sapovirus in nicaragua after implementation of universal rotavirus vaccination.
PLoS ONE9(May(5)),e98201.
Bucardo, F.,Rippinger, C.M.,Svensson,L.,Patton,J.T.,2012.Vaccine-derived NSP2segment in rotaviruses from vaccinated children with gastroenteritis in Nicaragua.Infect.Genet.Evol.12(August(6)),1282–1294.
Bugarcic,A.,Taylor,J.A.,2006.Rotavirus nonstructural glycoprotein NSP4is secreted from the apical surfaces of polarized epithelial cells.J.Virol.80(December(24)), 12343–12349.
Burke,B.,Desselberger,U.,1996.Rotavirus pathogenicity.Virology218(April(2)), 299–305.
Burns,J.W.,Siadat-Pajouh,M.,Krishnaney,A.A.,Greenberg,H.B.,1996.Protective effect of rotavirus VP6-speci?c IgA monoclonal antibodies that lack neutralizing activity.Science272(April(5258)),104–107.
Buttery,J.P.,Danchin,M.H.,Lee,K.J.,Carlin,J.B.,McIntyre,P.B.,Elliott,E.J.,Booy,R., Bines,J.E.,PAEDS/APSU Study Group,2011a.Intussusception following rotavirus vaccine administration:post-marketing surveillance in the National Immuniza-tion Program in Australia.Vaccine29(April(16)),3061–3066.
Buttery,J.P.,Lambert,S.B.,Grimwood,K.,Nissen,M.D.,Field,E.J.,Macartney,K.K., Akikusa,J.D.,Kelly,J.J.,Kirkwood,C.D.,2011b.Reduction in rotavirus-associated acute gastroenteritis following introduction of rotavirus vaccine into Australia’s National Childhood vaccine schedule.Pediatr.Infect.Dis.J.30(January(1 Suppl.)),S25–S29.
Campagna,M.,Budini,M.,Arnoldi,F.,Desselberger,U.,Allende,J.E.,Burrone,O.R., 2007.Impaired hyperphosphorylation of rotavirus NSP5in cells depleted of casein kinase1alpha is associated with the formation of viroplasms with altered morphology and a moderate decrease in virus replication.J.Gen.Virol.88 (October(Pt10)),2800–2810.
Campagna,M.,Eichwald,C.,Vascotto,F.,Burrone,O.R.,2005.RNA interference of rotavirus segment11mRNA reveals the essential role of NSP5in the virus replicative cycle.J.Gen.Virol.86(May(Pt5)),1481–1487.
Cao,D.,Barro,M.,Hoshino,Y.,2008.Porcine rotavirus bearing an aberrant gene stemming from an intergenic recombination of the NSP2and NSP5genes is defective and interfering.J.Virol.82(June(12)),6073–6077.
Carlin,J.B.,Macartney,K.K.,Lee,K.J.,Quinn,H.E.,Buttery,J.,Lopert,R.,Bines,J.,McIn-tyre,P.B.,2013.Intussusception risk and disease prevention associated with rotavirus vaccines in Australia’s National Immunization Program.Clin.Infect.
Dis.57(November(10)),1427–1434.
Centers for Disease Control Prevention(CDC),1999.Withdrawal of rotavirus vaccine recommendation.MMWR.Morb.Mortal.Wkly.Rep.48(November(43)),1007. Chacko,A.R.,Arifullah,M.,Sastri,N.P.,Jeyakanthan,J.,Ueno,G.,Sekar,K.,Read, R.J.,Dodson,E.J.,Rao,D.C.,Suguna,K.,2011.Novel pentameric structure of the diarrhea-inducing region of the rotavirus enterotoxigenic protein NSP4.J.Virol.
85(December(23)),12721–12732.
Charpilienne,A.,Lepault,J.,Rey,F.,Cohen,J.,2002.Identi?cation of rotavirus VP6 residues located at the interface with VP2that are essential for capsid assembly and transcriptase activity.J.Virol.76(August(15)),7822–7831.
Chattha,K.S.,Kandasamy,S.,Vlasova,A.N.,Saif,L.J.,Vitamin,A.,2013.de?ciency impairs adaptive B and T cell responses to a prototype monovalent attenuated human rotavirus vaccine and virulent human rotavirus challenge in a gnotobi-otic piglet model.PLoS ONE8(December(12)),e82966.
Chattopadhyay,S.,Basak,T.,Nayak,M.K.,Bhardwaj,G.,Mukherjee,A.,Bhowmick,R., Sengupta,S.,Chakrabarti,O.,Chatterjee,N.S.,Chawla-Sarkar,M.,2013.Identi?-cation of cellular calcium binding protein calmodulin as a regulator of rotavirus
A infection during comparative proteomic study.PLoS ONE8(2),e56655. Cheung,W.,Gill,M.,Esposito,A.,Kaminski,C.F.,Courousse,N.,Chwetzoff,S.,Trug-nan,G.,Keshavan,N.,Lever,A.,Desselberger,U.,2010.Rotaviruses associate with cellular lipid droplet components to replicate in viroplasms,and com-pounds disrupting or blocking lipid droplets inhibit viroplasm formation and viral replication.J.Virol.84(July(13)),6782–6798.
Cheuvart,B.,Neuzil,K.M.,Steele,A.D.,Cunliffe,N.,Madhi,S.A.,Karkada,N.,Han,
H.H.,Vinals,C.,2013.Association of serum anti-rotavirus immunoglobulin A
antibody seropositivity and protection against severe rotavirus gastroenteritis: Analysis of clinical trials of human rotavirus vaccine.Hum.Vaccin.Immunother.
10(November(2))(Epub ahead of print).
Chiarini,A.,Arista,S.,Giammanco,A.,Sinatra,A.,1983.Rotavirus persistence in cell cultures:selection of resistant cells in the presence of foetal calf serum.J.Gen.
Virol.64(May(Pt5)),1101–1110.
U.Desselberger/Virus Research190(2014)75–9689
Chizhikov,V.,Patton,J.T.,2000.A four-nucleotide translation enhancer in the3 -terminal consensus sequence of the nonpolyadenylated mRNAs of rotavirus.
RNA6(June(6)),814–825.
CHOICE Study Group,2001.Multicenter,randomized,double-blind clinical trial to evaluate the ef?cacy and safety of a reduced osmolarity oral rehydration salts solution in children with acute watery diarrhea.Pediatrics107(April(4)), 613–618.
Ciarlet,M.,Crawford,S.E.,Barone, C.,Bertolotti-Ciarlet, A.,Ramig,R.F.,Estes, M.K.,Conner,M.E.,1998.Subunit rotavirus vaccine administered parenterally to rabbits induces active protective immunity.J.Virol.72(November(11)), 9233–9246.
Ciccarelli,S.,Stol?,I.,Caramia,G.,2013.Management strategies in the treatment of neonatal and pediatric gastroenteritis.Infect.Drug Resist.6(October),133–161. Cohen,J.,Laporte,J.,Charpilienne,A.,Scherrer,R.,1979.Activation of rotavirus RNA polymerase by calcium chelation.Arch.Virol60(3–4),177–186.
Conner,M.E.,Zarley,C.D.,Hu,B.,Parsons,S.,Drabinski,D.,Greiner,S.,Smith,R.,Jiang,
B.,Corsaro,B.,Barniak,V.,Madore,H.P.,Crawford,S.,Estes,M.K.,1996.Virus-like
particles as a rotavirus subunit vaccine.J.Infect.Dis.174(September(Suppl.1)), S88–S92.
Contin,R.,Arnoldi,F.,Campagna,M.,Burrone,O.R.,2010.Rotavirus NSP5orches-trates recruitment of viroplasmic proteins.J.Gen.Virol.91(July(Pt7)), 1782–1793.
Contin,R.,Arnoldi,F.,Mano,M.,Burrone,O.R.,2011.Rotavirus replication requires
a functional proteasome for effective assembly of viroplasms.J.Virol.85(March
(6)),2781–2792.
Corrêa,N.B.,Penna,F.J.,Lima,F.M.,Nicoli,J.R.,Filho,L.A.,2011.Treatment of acute diarrhea with Saccharomyces boulardii in infants.J.Pediatr.Gastroenterol.Nutr.
53(November(5)),497–501.
Cortese,M.M.,Immergluck,L.C.,Held,M.,Jain,S.,Chan,T.,Grizas,A.P.,Khizer,S., Barrett,C.,Quaye,O.,Mijatovic-Rustempasic,S.,Gautam,R.,Bowen,M.D.,Moore, J.,Tate,J.E.,Parashar,U.D.,Vázquez,M.,2013.Effectiveness of monovalent and pentavalent rotavirus vaccine.Pediatrics132(July(1)),e25–e33.
Corthésy,B.,Benureau,Y.,Perrier,C.,Fourgeux,C.,Parez,N.,Greenberg,H.,Schwartz-Cornil,I.,2006.Rotavirus anti-VP6secretory immunoglobulin A contributes to protection via intracellular neutralization but not via immune exclusion.J.Virol.
80(November(21)),10692–10699.
Coulson,B.S.,Grimwood,K.,Hudson,I.L.,Barnes,G.L.,Bishop,R.F.,1992.Role of coproantibody in clinical protection of children during reinfection with rotavirus.J.Clin.Microbiol.30(July(7)),1678–1684.
Coulson,B.S.,Grimwood,K.,Masendycz,P.J.,Lund,J.S.,Mermelstein,N.,Bishop,R.F., Barnes,G.L.,https://www.360docs.net/doc/c88711488.html,parison of rotavirus immunoglobulin A coproconversion with other indices of rotavirus infection in a longitudinal study in childhood.J.
Clin.Microbiol.28(June(6)),1367–1374.
Coulson,B.S.,Londrigan,S.L.,Lee,D.J.,1997.Rotavirus contains integrin ligand sequences and a disintegrin-like domain that are implicated in virus entry into cells.Proc.Natl.Acad.Sci.U.S.A.94(May(10)),5389–5394.
Cowley,D.,Donato,C.M.,Roczo-Farkas,S.,Kirkwood,C.D.,2013.Novel G10P[14] rotavirus strain,Northern Territory,Australia.Emerg.Infect.Dis.19(August(8)), 1324–1327.
Crawford,S.E.,Estes,M.K.,2013.Viroporin-mediated calcium-activated autophagy.
Autophagy9(May(5)),797–798.
Crawford,S.E.,Estes,M.K.,Ciarlet,M.,Barone,C.,O’Neal,C.M.,Cohen,J.,Conner,M.E., 1999.Heterotypic protection and induction of a broad heterotypic neutralization response by rotavirus-like particles.J.Virol.73(June(6)),4813–4822. Crawford,S.E.,Hyser,J.M.,Utama,B.,Estes,M.K.,2012.Autophagy hijacked through viroporin-activated calcium/calmodulin-dependent kinase kinase-?signaling is required for rotavirus replication.Proc.Natl.Acad.Sci.U.S.A.109(December
(50)),E3405–E3413.
Crawford,S.E.,Labbé,M.,Cohen,J.,Burroughs,M.H.,Zhou,Y.J.,Estes,M.K.,1994.
Characterization of virus-like particles produced by the expression of rotavirus capsid proteins in insect cells.J.Virol.68(September(9)),5945–5952. Crawford,S.E.,Mukherjee,S.K.,Estes,M.K.,Lawton,J.A.,Shaw,A.L.,Ramig,R.F., Prasad,B.V.,2001.Trypsin cleavage stabilizes the rotavirus VP4spike.J.Virol.
75(July(13)),6052–6061.
Crawford,S.E.,Utama,B.,Hyser,J.M.,Broughman,J.R.,Estes,M.K.,2013.Rotavirus exploits lipid metabolism and energy production for replication.In:American Society for Virology Annual Meeting,Pennsylvania State University,University Park,PA,Abstracts;p.74(W2–6).
Criglar,J.,Greenberg,H.B.,Estes,M.K.,Ramig,R.F.,2011.Reconciliation of rotavirus temperature-sensitive mutant collections and assignment of reassortment groups D,J,and K to genome segments.J.Virol.85(May(10)),5048–5060. Criglar,J.M.,Hu,L.,Crawford,S.E.,Hyser,J.M.,Broughman,J.R.,Prasad,B.V.,Estes, M.K.,2014.A novel form of rotavirus NSP2and phosphorylation-dependent NSP2-NSP5interactions are associated with viroplasm assembly.J.Virol.88 (January(2)),786–798.
da Silva,M.F.,Tort,L.F.,Goméz,M.M.,Assis,R.M.,Volot?o Ede,M.,de Mendonc?a,M.C., Bello,G.,Leite,J.P.,2011.VP7gene of human rotavirus A genotype G5:phylo-genetic analysis reveals the existence of three different lineages worldwide.J.
Med.Virol.83(February(2)),357–366.
Deal,E.M.,Lahl,K.,Narváez,C.F.,Butcher,E.C.,Greenberg,H.B.,2013.Plasmacytoid dendritic cells promote rotavirus-induced human and murine B cell responses.
J.Clin.Invest.123(June(6)),2464–2474.
De Grazia,S.,Bonura,F.,Colomba,C.,Cascio,A.,Di Bernardo,F.,Collura,A.,Terra-nova,D.M.,Martella,V.,Giammanco,G.M.,2014.Data mining from a27-years rotavirus surveillance in Palermo,Italy.Infect.Genet.Evol.(March),pii:S1567-1348(14)00083-5.De Lorenzo,G.,Eichwald,C.,Schraner,E.M.,Nicolin,V.,Bortul,R.,Mano,M.,Burrone, O.R.,Arnoldi,F.,2012.Production of in vivo-biotinylated rotavirus particles.J.
Gen.Virol.93(7),1474–1482.
Delmas,O.,Breton,M.,Sapin,C.,Le Bivic,A.,Colard,O.,Trugnan,G.,2007.Het-erogeneity of Raft-type membrane microdomains associated with VP4,the rotavirus spike protein,in Caco-2and MA104cells.J.Virol.81(February(4)), 1610–1618.
Dennehy,P.H.,2013.Treatment and prevention of rotavirus infection in children.
Curr.Infect.Dis.Rep.15(June(3)),242–250.
Dennehy,P.H.,Cortese,M.M.,Bégué,R.E.,Jaeger,J.L.,Roberts,N.E.,Zhang,R.,Rhodes, P.,Gentsch,J.,Ward,R.,Bernstein,D.I.,Vitek,C.,Bresee,J.S.,Staat,M.A.,2006.
A case-control study to determine risk factors for hospitalization for rotavirus
gastroenteritis in U.S.children.Pediatr.Infect.Dis.J.25(December(12)), 1123–1131.
Desai,R.,Curns,A.T.,Steiner,C.A.,Tate,J.E.,Patel,M.M.,Parashar,U.D.,2012.All-cause gastroenteritis and rotavirus-coded hospitalizations among US children, 2000–2009.Clin.Infect.Dis.55(August(4)),e28–e34.
Desselberger,U.,1996.Genome rearrangements of rotaviruses.Adv.Virus Res.46, 69–95.
Desselberger,U.,1998.Prospects for vaccines against rotaviruses.Rev.Med.Virol.8 (January(1)),43–52.
Desselberger,U.,1999.Rotavirus infections:guidelines for treatment and preven-tion.Drugs58(September(3)),447–452.
Desselberger,U.,Gray,J.,2013.Viral gastroenteritis.Medicine(Baltimore).41(12), 700–704.
Desselberger,U.,Huppertz,H.I.,2011.Immune responses to rotavirus infection and vaccination and associated correlates of protection.J.Infect.Dis.203(January
(2)),188–195.
Desselberger,U.,Richards,J.,Tchertanov,L.,Lepault,J.,Lever,A.,Burrone,O.,Cohen, J.,2013.Further characterisation of rotavirus cores:ss(+)RNAs can be packaged in vitro but packaging lacks sequence speci?city.Virus Res.178(December(2)), 252–263.
Díaz-Salinas,M.A.,Silva-Ayala,D.,López,S.,Arias,C.F.,2014.Rotaviruses reach late endosomes and require the cation-dependent mannose-6-phosphate receptor and the activity of cathepsin proteases to enter the cell.J.Virol.(February)(Epub ahead of print).
Donato,C.M.,Zhang,Z.A.,Donker,N.C.,Kirkwood,C.D.,2014.Characterization of G2P[4]rotavirus strains associated with increased detection in Australian states using the RotaTeq?vaccine during the2010-2011surveillance period.Infect.
Genet.Evol.(May),https://www.360docs.net/doc/c88711488.html,/10.1016/j.meegid.2014.05.020,pii:S1567-1348(14)00189-0(Epub ahead of print).
Donker,N.C.,Boniface,K.,Kirkwood,C.D.,2011.Phylogenetic analysis of rotavirus A NSP2gene sequences and evidence of intragenic recombination.Infect.Genet.
Evol.11(October(7)),1602–1607.
Dormitzer,P.R.,Sun,Z.Y.,Blixt,O.,Paulson,J.C.,Wagner,G.,Harrison,S.C.,2002a.
Speci?city and af?nity of sialic acid binding by the rhesus rotavirus VP8*core.
J.Virol.76(October(20)),10512–10517.
Dormitzer,P.R.,Sun,Z.Y.,Wagner,G.,Harrison,S.C.,2002b.The rhesus rotavirus VP4 sialic acid binding domain has a galectin fold with a novel carbohydrate binding site.EMBO J.21(March(5)),885–897.
Dubin,G.,Toussaint,J.F.,Cassart,J.P.,Howe,B.,Boyce,D.,Friedland,L.,Abu-Elyazeed, R.,Poncelet,S.,Han,H.H.,Debrus,S.,2013.Investigation of a regulatory agency enquiry into potential porcine circovirus type1contamination of the human rotavirus vaccine,Rotarix TM:approach and outcome.Hum.Vaccin.Immunother.
9(August(11))(Epub ahead of print).
Ebina,T.,1996.Prophylaxis of rotavirus gastroenteritis using immunoglobulin.Arch.
Virol.Suppl.12,217–223.
Eichwald,C.,Arnoldi,F.,Laimbacher,A.S.,Schraner,E.M.,Fraefel,C.,Wild,P.,Bur-rone,O.R.,Ackermann,M.,2012.Rotavirus viroplasm fusion and perinuclear localization are dynamic processes requiring stabilized microtubules.PLoS ONE 7(10),e47947.
Eichwald, C.,Rodriguez,J.F.,Burrone,O.R.,2004.Characterization of rotavirus NSP2/NSP5interactions and the dynamics of viroplasm formation.J.Gen.Virol.
85(March(Pt3)),625–634.
Esona,M.D.,Mijatovic-Rustempasic,S.,Yen,C.,Parashar,U.D.,Gentsch,J.R.,Bowen, M.D.,Larussa,P.,2014.Detection of PCV-2DNA in stool samples from infants vaccinated with RotaTeq?.Hum.Vaccin.Immunother.10(January(1)),25–32. Esposito,D.H.,Holman,R.C.,Haberling,D.L.,Tate,J.E.,Podewils,L.J.,Glass,R.I., Parashar,U.,2011.Baseline estimates of diarrhea-associated mortality among United States children before rotavirus vaccine introduction.Pediatr.Infect.Dis.
J.30(November(11)),942–947.
Essere,B.,Yver,M.,Gavazzi,C.,Terrier,O.,Isel,C.,Fournier,E.,Giroux,F.,Textoris, J.,Julien,T.,Socratous,C.,Rosa-Calatrava,M.,Lina,B.,Marquet,R.,Moules,V., 2013.Critical role of segment-speci?c packaging signals in genetic reassort-ment of in?uenza A viruses.Proc.Natl.Acad.Sci.U.S.A.110(October(40)), E3840–E3848.
Estes,M.K.,Atmar,R.L.,2003.Viral pathogens in the intestine.In:Hecht,G.(Ed.), Microbial Pathogenesis and the Intestinal Epithelial Cell.ASM Press,Washing-ton,DC,pp.525–545.
Estes,M.K.,Graham,D.Y.,1980.Establishment of rotavirus persistent infection in cell culture.Arch.Virol65(2),187–192.
Estes,M.K.,Graham,D.Y.,Smith,E.M.,Gerba,C.P.,1979.Rotavirus stability and inactivation.J.Gen.Virol.43(May(2)),403–409.
Estes,M.K.,Greenberg,H.B.,2013.Rotaviruses.In:Knipe,D.M.,Howley,P.M.,et al.
(Eds.),Fields Virology.,6th ed.Wolters Kluwer Health/Lippincott Williams& Wilkins,Philadelphia,PA,pp.1347–1401.
90U.Desselberger/Virus Research190(2014)75–96
Estes,M.K.,Graham,D.Y.,Mason,B.B.,1981.Proteolytic enhancement of rotavirus infectivity:molecular mechanisms.J.Virol.39(September(3)),879–888. Estes,M.K.,Morris,A.P.,1999.A viral enterotoxin.A new mechanism of virus-induced pathogenesis.Adv.Exp.Med.Biol.473,73–82.
Estrozi,L.F.,Settembre,E.C.,Goret,G.,McClain,B.,Zhang,X.,Chen,J.Z.,Grigorieff, N.,Harrison,S.C.,2013.Location of the dsRNA-dependent polymerase,VP1,in rotavirus particles.J.Mol.Biol.425(January(1)),124–132.
Fabbretti,E.,Afrikanova,I.,Vascotto,F.,Burrone,O.R.,1999.Two non-structural rotavirus proteins,NSP2and NSP5,form viroplasm-like structures in vivo.J.
Gen.Virol.80(February(Pt2)),333–339.
Fang,S.B.,Lee,H.C.,Hu,J.J.,Hou,S.Y.,Liu,H.L.,Fang,H.W.,2009.Dose-dependent effect of Lactobacillus rhamnosus on quantitative reduction of faecal rotavirus shedding in children.J.Trop.Pediatr.55(October(5)),297–301.
Fenaux,M.,Cuadras,M.A.,Feng,N.,Jaimes,M.,Greenberg,H.B.,2006.Extraintestinal spread and replication of a homologous EC rotavirus strain and a heterologous rhesus rotavirus in BALB/c mice.J.Virol.80(June(11)),5219–5232.
Feng,N.,Franco,M.A.,Greenberg,H.B.,1997.Murine model of rotavirus infection.
Adv.Exp.Med.Biol.412,233–240.
Feng,N.,Kim,B.,Fenaux,M.,Nguyen,H.,Vo,P.,Omary,M.B.,Greenberg,H.B.,2008.
Role of interferon in homologous and heterologous rotavirus infection in the intestines and extraintestinal organs of suckling mice.J.Virol.82(August(15)), 7578–7590.
Feng,N.,Lawton,J.A.,Gilbert,J.,Kuklin,N.,Vo,P.,Prasad,B.V.,Greenberg,H.B.,2002.
Inhibition of rotavirus replication by a non-neutralizing,rotavirus VP6-speci?c IgA mAb.J.Clin.Invest.109(May(9)),1203–1213.
Feng,N.,Sen,A.,Nguyen,H.,Vo,P.,Hoshino,Y.,Deal,E.M.,Greenberg,H.B.,2009.
Variation in antagonism of the interferon response to rotavirus NSP1results in differential infectivity in mouse embryonic?broblasts.J.Virol.83(July(14)), 6987–6994.
Feng,N.,Sen,A.,Wolf,M.,Vo,P.,Hoshino,Y.,Greenberg,H.B.,2011.Roles of VP4and NSP1in determining the distinctive replication capacities of simian rotavirus RRV and bovine rotavirus UK in the mouse biliary tract.J.Virol.85(March(6)), 2686–2694.
Feng,N.,Yasukawa,L.L.,Sen,A.,Greenberg,H.B.,2013.Permissive replication of homologous murine rotavirus in the mouse intestine is primarily regulated by VP4and NSP1.J.Virol.87(August(15)),8307–8316.
Finkbeiner,S.R.,Allred,A.F.,Tarr,P.I.,Klein,E.J.,Kirkwood,C.D.,Wang,D.,2008.
Metagenomic analysis of human diarrhea:viral detection and discovery.PLoS Pathog.4(February(2)),e1000011.
Finkbeiner,S.R.,Zeng,X.L.,Utama, B.,Atmar,R.L.,Shroyer,N.F.,Estes,M.K., 2012.Stem cell-derived human intestinal organoids as an infection model for rotaviruses.MBio3(July(4)),e00159–e212.
Fiore,L.,Greenberg,H.B.,Mackow,E.R.,1991.The VP8fragment of VP4is the rhesus rotavirus hemagglutinin.Virology181(April(2)),553–563.
Fischer,T.K.,Gentsch,J.R.,2004.Rotavirus typing methods and algorithms.Rev.Med.
Virol.14(March–April(2)),71–82.
Fischer,T.K.,Viboud,C.,Parashar,U.,Malek,M.,Steiner,C.,Glass,R.,Simonsen,L., 2007.Hospitalizations and deaths from diarrhea and rotavirus among children of<5years of age in the United States,1993–2003.J.Infect.Dis.195(April(8)), 1117–1125.
Fleming,F.E.,B?hm,R.,Dang,V.T.,Holloway,G.,Haselhorst,T.,Madge,P.D.,Dev-eryshetty,J.,Yu,X.,Blanchard,H.,von Itzstein,M.,Coulson,B.S.,2014.Relative roles of GM1ganglioside,N-acylneuraminic acids and?2?1integrin in mediat-ing rotavirus infection.J.Virol.(February)(Epub ahead of print).
Flewett,T.H.,Bryden,A.S.,Davies,H.,1973.Virus particles in https://www.360docs.net/doc/c88711488.html,ncet 2(December(7844)),1497.
Flewett,T.H.,Bryden,A.S.,Davies,H.,Woode,G.N.,Bridger,J.C.,Derrick,J.M.,1974.
Relation between viruses from acute gastroenteritis of children and newborn https://www.360docs.net/doc/c88711488.html,ncet2(July(7872)),61–63.
Franco,M.A.,Angel,J.,Greenberg,H.B.,2006.Immunity and correlates of protection for rotavirus vaccines.Vaccine24(April(15)),2718–2731.
Franco,M.A.,Greenberg,H.B.,1997.Immunity to rotavirus in T cell de?cient mice.
Virology238(November(2)),169–179.
Garaicoechea,L.,Olichon,A.,Marcoppido,G.,Wigdorovitz,A.,Mozgovoj,M.,Saif, L.,Surrey,T.,Parre?no,V.,2008.Llama-derived single-chain antibody fragments directed to rotavirus VP6protein possess broad neutralizing activity in vitro and confer protection against diarrhea in mice.J.Virol.82(October(19)), 9753–9764.
Gardet,A.,Breton,M.,Fontanges,P.,Trugnan,G.,Chwetzoff,S.,2006.Rotavirus spike protein VP4binds to and remodels actin bundles of the epithelial brush border into actin bodies.J.Virol.80(April(8)),3947–3956.
Gasta?naduy,P.A.,Curns,A.T.,Parashar,U.D.,Lopman,B.A.,2013.Gastroenteritis hospitalizations in older children and adults in the United States before and after implementation of infant rotavirus vaccination.JAMA310(August(8)), 851–853.
Gaunt,E.R.,Cheung,W.,Richards,J.E.,Lever,A.,Desselberger,U.,2013a.Inhibition of rotavirus replication by downregulation of fatty acid synthesis.J.Gen.Virol.
94(June(Pt6)),1310–1317,Erratum in:J.Gen.Virol.,2013,94(September(Pt
9)),2140.
Gaunt, E.R.,Zhang,Q.,Cheung,W.,Wakelam,M.J.,Lever, A.M.,Desselberger, U.,2013b.Lipidome analysis of rotavirus-infected cells con?rms the close interaction of lipid droplets with viroplasms.J.Gen.Virol.94(July(Pt7)), 1576–1586.
Ge,Y.,Mansell,A.,Ussher,J.E.,Brooks,A.E.,Manning,K.,Wang,C.J.,Taylor,J.A., 2013.Rotavirus NSP4triggers secretion of proin?ammatory cytokines from macrophages via Toll-like receptor2.J.Virol.87(October(20)),11160–11167.Gentsch,J.R.,Glass,R.I.,Woods,P.,Gouvea,V.,Gorziglia,M.,Flores,J.,Das,B.K.,Bhan, M.K.,1992.Identi?cation of group A rotavirus gene4types by polymerase chain reaction.J.Clin.Microbiol.30(June(6)),1365–1373.
Gentsch,J.R.,Laird,A.R.,Bielfelt,B.,Grif?n,D.D.,Banyai,K.,Ramachandran,M.,Jain, V.,Cunliffe,N.A.,Nakagomi,O.,Kirkwood,C.D.,Fischer,T.K.,Parashar,U.D.,Bre-see,J.S.,Jiang,B.,Glass,R.I.,2005.Serotype diversity and reassortment between human and animal rotavirus strains:implications for rotavirus vaccine pro-grams.J.Infect.Dis.192(September(Suppl.1)),S146–S159.
Georges-Courbot,M.C.,Monges,J.,Siopathis,M.R.,Roungou,J.B.,Gresenguet,G.,Bel-lec,L.,Bouquety,J.C.,Lanckriet,C.,Cadoz,M.,Hessel,L.,et al.,1991.Evaluation of the ef?cacy of a low-passage bovine rotavirus(strain WC3)vaccine in children in Central Africa.Res.Virol.142(September–October(5)),405–411. Giaquinto,C.,Dominiak-Felden,G.,Van Damme,P.,Myint,T.T.,Maldonado,Y.A., Spoulou,V.,Mast,T.C.,Staat,M.A.,2011.Summary of effectiveness and impact of rotavirus vaccination with the oral pentavalent rotavirus vaccine:a systematic review of the experience in industrialized countries.Hum.Vaccin.7(July(7)), 734–748.
Gilger,M.A.,Matson,D.O.,Conner,M.E.,Rosenblatt,H.M.,Finegold,M.J.,Estes,M.K., 1992.Extraintestinal rotavirus infections in children with immunode?ciency.J.
Pediatr.120(June(6)),912–917.
Glass,R.I.,Bresee,J.S.,Parashar,U.D.,Jiang,B.,Gentsch,J.,2004.The future of rotavirus vaccines:a major setback leads to new https://www.360docs.net/doc/c88711488.html,ncet363(May (9420)),1547–1550.
Glass,R.I.,Parashar,U.D.,2014.Rotavirus vaccines–balancing intussusception risks and health bene?ts.N.Engl.J.Med.370(February(6)),568–570.
Glass,R.I.,Parashar,U.,Patel,M.,Gentsch,J.,Jiang,B.,2014.Rotavirus vaccines: successes and challenges.J.Infect.68(January(Suppl.1)),S9–S18.
Gleizes,O.,Desselberger,U.,Tatochenko,V.,Rodrigo,C.,Salman,N.,Mezner,Z., Giaquinto,C.,Grimprel,E.,2006.Nosocomial rotavirus infection in European countries:a review of the epidemiology,severity and economic burden of hospital-acquired rotavirus disease.Pediatr.Infect.Dis.J.25(January(1Suppl.)), S12–S21.
Gómara,M.I.,Green,J.,Gray,J.,2000.Methods of rotavirus detection,sero-and geno-typing,sequencing,and phylogenetic analysis.Methods Mol.Med.34,189–216. González,A.M.,Azevedo,M.S.,Jung,K.,Vlasova,A.,Zhang,W.,Saif,L.J.,2010.Innate immune responses to human rotavirus in the neonatal gnotobiotic piglet disease model.Immunology131(October(2)),242–256.
Gonzalez,A.M.,Jaimes,M.C.,Cajiao,I.,Rojas,O.L.,Cohen,J.,Pothier,P.,Kohli,E., Butcher,E.C.,Greenberg,H.B.,Angel,J.,Franco,M.A.,2003.Rotavirus-speci?c
B cells induced by recent infection in adults and children predominantly
express the intestinal homing receptor alpha4beta7.Virology305(January(1)), 93–105.
González,R.A.,Espinosa,R.,Romero,P.,López,S.,Arias,C.F.,2000.Relative localiza-tion of viroplasmic and endoplasmic reticulum-resident rotavirus proteins in infected cells.Arch.Virol.145(9),1963–1973.
Gouet,P.,Diprose,J.M.,Grimes,J.M.,Malby,R.,Burroughs,J.N.,Zientara,S.,Stuart,
D.I.,Mertens,P.P.,1999.The highly ordered double-stranded RNA genome of
bluetongue virus revealed by crystallography.Cell97(May(4)),481–490. Gouvea,V.,Glass,R.I.,Woods,P.,Taniguchi,K.,Clark,H.F.,Forrester,B.,Fang,Z.Y., 1990.Polymerase chain reaction ampli?cation and typing of rotavirus nucleic acid from stool specimens.J.Clin.Microbiol.28(February(2)),276–282. Graff,J.W.,Ettayebi,K.,Hardy,M.E.,2009.Rotavirus NSP1inhibits NFkappaB acti-vation by inducing proteasome-dependent degradation of beta-TrCP:a novel mechanism of IFN antagonism.PLoS Pathog.5(January(1)),e1000280.
Graff,J.W.,Ewen,J.,Ettayebi,K.,Hardy,M.E.,2007.Zinc-binding domain of rotavirus NSP1is required for proteasome-dependent degradation of IRF3and autoregu-latory NSP1stability.J.Gen.Virol.88(February(Pt2)),613–620.
Graff,J.W.,Mitzel,D.N.,Weisend,C.M.,Flenniken,M.L.,Hardy,M.E.,2002.Interferon regulatory factor3is a cellular partner of rotavirus NSP1.J.Virol.76(September
(18)),9545–9550.
Graham,D.Y.,Dufour,G.R.,Estes,M.K.,1987.Minimal infective dose of rotavirus.
Arch.Virol92(3–4),261–271.
Graham,K.L.,Halasz,P.,Tan,Y.,Hewish,M.J.,Takada,Y.,Mackow,E.R.,Robinson, M.K.,Coulson,B.S.,2003.Integrin-using rotaviruses bind alpha2beta1integ-rin alpha2I domain via VP4DGE sequence and recognize alphaXbeta2and alphaVbeta3by using VP7during cell entry.J.Virol.77(September(18)), 9969–9978.
Grandy,G.,Medina,M.,Soria,R.,Terán,C.G.,Araya,M.,2010.Probiotics in the treat-ment of acute rotavirus diarrhoea.A randomized,double-blind,controlled trial using two different probiotic preparations in Bolivian children.BMC Infect.Dis.
10(August),253.
Greenberg,H.B.,2011.Rotavirus vaccination and intussusception–act two.N.Engl.
J.Med.364(June(24)),2354–2355.
Greenberg,H.B.,Estes,M.K.,2009.Rotaviruses:from pathogenesis to vaccination.
Gastroenterology136(May(6)),1939–1951.
Groft,C.M.,Burley,S.K.,2002.Recognition of eIF4G by rotavirus NSP3reveals a basis for mRNA circularization.Mol.Cell9(June(6)),1273–1283.
Guarino,A.,Dupont,C.,Gorelov,A.V.,Gottrand,F.,Lee,J.K.,Lin,Z.,Lo Vecchio,A., Nguyen,T.D.,Salazar-Lindo,E.,2012.The management of acute diarrhea in chil-dren in developed and developing areas:from evidence base to clinical practice.
Expert Opin.Pharmacother.13(January(1)),17–26.
Guerrero,C.A.,Bouyssounade,D.,Zárate,S.,Isa,P.,López,T.,Espinosa,R.,Romero,P., Méndez,E.,López,S.,Arias,C.F.,2002.Heat shock cognate protein70is involved in rotavirus cell entry.J.Virol.76(April(8)),4096–4102.
Guo,C.T.,Nakagomi,O.,Mochizuki,M.,Ishida,H.,Kiso,M.,Ohta,Y.,Suzuki,T., Miyamoto,D.,Hidari,K.I.,Suzuki,Y.,1999.Ganglioside GM(1a)on the cell surface
U.Desselberger/Virus Research190(2014)75–9691
is involved in the infection by human rotavirus KUN and MO strains.J.Biochem.
126(October(4)),683–688.
Gutiérrez,M.,Isa,P.,Sánchez-San Martin,C.,Pérez-Vargas,J.,Espinosa,R.,Arias,
C.F.,López,S.,2010.Different rotavirus strains enter MA104cells through dif-
ferent endocytic pathways:the role of clathrin-mediated endocytosis.J.Virol.
84(September(18)),9161–9169.
Haber,P.,Chen,R.T.,Zanardi,L.R.,Mootrey,G.T.,English,R.,Braun,M.M.,2004.VAERS Working Group,An analysis of rotavirus vaccine reports to the vaccine adverse event reporting system:more than intussusception alone?Pediatrics113(April
(4)),e353–e359.
Haber,P.,Patel,M.,Pan,Y.,Baggs,J.,Haber,M.,Museru,O.,Yue,X.,Lewis,P.,Deste-fano,F.,Parashar,U.D.,2013.Intussusception after rotavirus vaccines reported to US VAERS,2006–2012.Pediatrics131(June(6)),1042–1049.
Hagbom,M.,Istrate,C.,Engblom,D.,Karlsson,T.,Rodriguez-Diaz,J.,Buesa,J.,Taylor, J.A.,Loitto,V.M.,Magnusson,K.E.,Ahlman,H.,Lundgren,O.,Svensson,L.,2011.
Rotavirus stimulates release of serotonin(5-HT)from human enterochromaf-?n cells and activates brain structures involved in nausea and vomiting.PLoS Pathog.7(July(7)),e1002115.
Hagbom,M.,Sharma,S.,Lundgren,O.,Svensson,L.,2012.Towards a human rotavirus disease model.Curr.Opin.Virol.2(August(4)),408–418.
Harb,M.,Becker,M.M.,Vitour,D.,Baron,C.H.,Vende,P.,Brown,S.C.,Bolte,S.,Arold, S.T.,Poncet,D.,2008.Nuclear localization of cytoplasmic poly(A)-binding pro-tein upon rotavirus infection involves the interaction of NSP3with eIF4G and RoXaN.J.Virol.82(November(22)),11283–11293.
Haselhorst,T.,Fleming,F.E.,Dyason,J.C.,Hartnell,R.D.,Yu,X.,Holloway,G.,Sante-goets,K.,Kiefel,M.J.,Blanchard,H.,Coulson,B.S.,von Itzstein,M.,2009.Sialic acid dependence in rotavirus host cell invasion.Nat.Chem.Biol.5(February(2)), 91–93.
He,B.,Yang,F.,Yang,W.,Zhang,Y.,Feng,Y.,Zhou,J.,Xie,J.,Feng,Y.,Bao,X.,Guo,H., Li,Y.,Xia,L.,Li,N.,Matthijnssens,J.,Zhang,H.,Tu,C.,2013.Characterization of
a novel G3P[3]rotavirus isolated from a lesser horseshoe bat:a distant relative
of feline/canine rotaviruses.J.Virol.87(November(22)),12357–12366. Hemming,M.,R?s?nen,S.,Huhti,L.,Paloniemi,M.,Salminen,M.,Vesikari,T., 2013.Major reduction of rotavirus,but not norovirus,gastroenteritis in chil-dren seen in hospital after the introduction of RotaTeq vaccine into the National Immunization Programme in Finland.Eur.J.Pediatr.172(June(6)), 739–746.
Hemming,M.,Vesikari,T.,2013a.Genetic diversity of G1P[8]rotavirus VP7and VP8* antigens in Finland over a20-year period:No evidence for selection pressure by universal mass vaccination with RotaTeq?vaccine.Infect.Genet.Evol.19 (October),51–58.
Hemming,M.,Vesikari,T.,2013b.Detection of Rotateq?vaccine-derived double reassortant rotavirus in a7-year-old child with acute gastroenteritis.Pediatr.
Infect.Dis.J.(December)(Epub ahead of print).
Herrmann,J.E.,Chen,S.C.,Fynan,E.F.,Santoro,J.C.,Greenberg,H.B.,Wang,S.,Robin-son,H.L.,1996.Protection against rotavirus infections by DNA vaccination.J.
Infect.Dis.174(September(Suppl.1)),S93–S97.
Hertel,P.M.,Crawford,S.E.,Bessard,B.C.,Estes,M.K.,2013.Prevention of cholestasis in the murine rotavirus-induced biliary atresia model using passive immu-nization and nonreplicating virus-like particles.Vaccine31(November(48)), 5778–5784.
Holloway,G.,Coulson,B.S.,2013.Innate cellular responses to rotavirus infection.J.
Gen.Virol.94(June(Pt6)),1151–1160.
Holloway,G.,Dang,V.T.,Jans,D.A.,Coulson,B.S.,2014.Rotavirus inhibits interferon-induced STAT nuclear translocation by a mechanism that acts after STAT binding to importin-?.J.Gen.Virol.(May),https://www.360docs.net/doc/c88711488.html,/10.1099/vir.0.064063-0 (Epub ahead of print).
Holloway,G.,Truong,T.T.,Coulson,B.S.,2009.Rotavirus antagonizes cellular antivi-ral responses by inhibiting the nuclear accumulation of STAT1,STAT2,and NF-kappaB.J.Virol.83(May(10)),4942–4951.
Hou,Z.,Huang,Y.,Huan,Y.,Pang,W.,Meng,M.,Wang,P.,Yang,M.,Jiang,L.,Cao, X.,Wu,K.K.,2008.Anti-NSP4antibody can block rotavirus-induced diarrhea in mice.J.Pediatr.Gastroenterol.Nutr.46(April(4)),376–385.
Hrdy,D.B.,1987.Epidemiology of rotaviral infection in adults.Rev.Infect.Dis.9 (May–June(3)),461–469.
Hu,L.,Crawford,S.E.,Czako,R.,Cortes-Pen?eld,N.W.,Smith,D.F.,Le Pendu,J.,Estes, M.K.,Prasad,B.V.,2012.Cell attachment protein VP8*of a human rotavirus speci?cally interacts with A-type histo-blood group antigen.Nature485(April (7397)),256–259.
Huang,P.,Xia,M.,Tan,M.,Zhong,W.,Wei,C.,Wang,L.,Morrow,A.,Jiang,X.,2012.
Spike protein VP8*of human rotavirus recognizes histo-blood group antigens in a type-speci?c manner.J.Virol.86(May(9)),4833–4843.
Hundley,F.,Biryahwaho,B.,Gow,M.,Desselberger,U.,1985.Genome rearrange-ments of bovine rotavirus after serial passage at high multiplicity of infection.
Virology143(May(1)),88–103.
Hundley,F.,McIntyre,M.,Clark,B.,Beards,G.,Wood,D.,Chrystie,I.,Desselberger, U.,1987.Heterogeneity of genome rearrangements in rotaviruses isolated from
a chronically infected immunode?cient child.J.Virol.61(November(11)),
3365–3372.
Hung,T.,Chen,G.M.,Wang,C.G.,Yao,H.L.,Fang,Z.Y.,Chao,T.X.,Chou,Z.Y.,Ye, W.,Chang,X.J.,Den,S.S.,et al.,1984.Waterborne outbreak of rotavirus diar-rhoea in adults in China caused by a novel https://www.360docs.net/doc/c88711488.html,ncet1(May(8387)), 1139–1142.
Hung,T.,Chen,G.M.,Wang,C.G.,Chou,Z.Y.,Chao,T.X.,Ye,W.W.,Yao,H.L.,Meng, K.H.,1983.Rotavirus-like agent in adult non-bacterial diarrhoea in https://www.360docs.net/doc/c88711488.html,ncet 2(November(8358)),1078–1079.Hyser,J.M.,Collinson-Pautz,M.R.,Utama, B.,Estes,M.K.,2010.Rotavirus dis-rupts calcium homeostasis by NSP4viroporin activity.MBio1(November(5)), e00265–e00310.
Hyser,J.M.,Utama,B.,Crawford,S.E.,Broughman,J.R.,Estes,M.K.,2013.Activation of the endoplasmic reticulum calcium sensor STIM1and store-operated calcium entry by rotavirus requires NSP4viroporin activity.J.Virol.87(December(24)), 13579–13588.
Hyser,J.M.,Utama,B.,Crawford,S.E.,Estes,M.K.,2012.Genetic divergence of rotavirus nonstructural protein4results in distinct serogroup-speci?c viroporin activity and intracellular punctate structure morphologies.J.Virol.86(May(9)), 4921–4934.
Ianiro,G.,Heylen,E.,Delogu,R.,Zeller,M.,Matthijnssens,J.,Ruggeri,F.M.,Van Ranst, M.,Fiore,L.,2013.Genetic diversity of G9P[8]rotavirus strains circulating in Italy in2007and2010as determined by whole genome sequencing.Infect.Genet.
Evol.16(June),426–432.
Imbert-Marcille,B.M.,Barbé,L.,Dupé,M.,Le Moullac-Vaidye,B.,Besse,B.,Peltier,
C.,Ruvo?n-Clouet,N.,Le Pendu,J.,2014.A FUT2gene common polymorphism
determines resistance to rotavirus A of the P[8]genotype.J.Infect.Dis.209(April
(8)),1227–1230.
Isa,P.,Arias,C.F.,López,S.,2006.Role of sialic acids in rotavirus infection.Glycoconj.
J.23(February(1–2)),27–37.
Isa,P.,Realpe,M.,Romero,P.,López,S.,Arias,C.F.,2004.Rotavirus RRV associates with lipid membrane microdomains during cell entry.Virology322(May(2)), 370–381,Erratum in:Virology,2004,328(October(1)),158.
Iturriza-Gómara,M.,Dallman,T.,Bányai,K.,B?ttiger,B.,Buesa,J.,Diedrich,S.,Fiore, L.,Johansen,K.,Koopmans,M.,Korsun,N.,Koukou,D.,Kroneman,A.,László,
B.,Lappalainen,M.,Maunula,L.,Marques,A.M.,Matthijnssens,J.,Midgley,S.,
Mladenova,Z.,Nawaz,S.,Poljsak-Prijatelj,M.,Pothier,P.,Ruggeri,F.M.,Sanchez-Fauquier,A.,Steyer,A.,Sidaraviciute-Ivaskeviciene,I.,Syriopoulou,V.,Tran,A.N., Usonis,V.,VAN Ranst,M.,DE Rougemont,A.,Gray,J.,2011.Rotavirus genotypes co-circulating in Europe between2006and2009as determined by EuroRotaNet,
a pan-European collaborative strain surveillance network.Epidemiol.Infect.139
(June(6)),895–909.
Iturriza-Gomara,M.,Desselberger,U.,Gray,J.,2003.Molecular epidemiology of rotaviruses:genetic mechanisms associated with diversity.In:Desselberger,U., Gray,J.(Eds.),Viral Gastroenteritis.Elsevier Science,Amsterdam,pp.317–344. Iturriza-Gómara,M.,Green,J.,Brown,D.W.,Desselberger,U.,Gray,J.J.,2000.Diver-sity within the VP4gene of rotavirus P[8]strains:implications for reverse transcription-PCR genotyping.J.Clin.Microbiol.38(February(2)),898–901. Iturriza-Gómara,M.,Isherwood,B.,Desselberger,U.,Gray,J.,2001.Reassortment in vivo:driving force for diversity of human rotavirus strains isolated in the United Kingdom between1995and1999.J.Virol.75(April(8)),3696–3705.
Iturriza-Gómara,M.,Kang,G.,Gray,J.,2004.Rotavirus genotyping:keeping up with an evolving population of human rotaviruses.J.Clin.Virol.31(December(4)), 259–265.
Jayaram,H.,Estes,M.K.,Prasad,B.V.,2004.Emerging themes in rotavirus cell entry, genome organization,transcription and replication.Virus Res.101(April(1)), 67–81.
Jere,K.C.,Mlera,L.,Page,N.A.,van Dijk,A.A.,O’Neill,H.G.,2011.Whole genome analysis of multiple rotavirus strains from a single stool specimen using sequence-independent ampli?cation and454?pyrosequencing reveals evi-dence of intergenotype genome segment recombination.Infect.Genet.Evol.11 (December(8)),2072–2082.
Jiang,B.,Gentsch,J.R.,Glass,R.I.,2002.The role of serum antibodies in the pro-tection against rotavirus disease:an overview.Clin.Infect.Dis.34(May(10)), 1351–1361.
Jiang,B.,Gentsch,J.R.,Glass,R.I.,2008a.Inactivated rotavirus vaccines:a priority for accelerated vaccine development.Vaccine26(December(52)),6754–6758. Jiang,B.,Wang,Y.,Glass,R.I.,2013.Does a monovalent inactivated human rotavirus vaccine induce heterotypic immunity?Evidence from animal studies.Hum.Vac-cin.Immunother.9(August(8)),1634–1637.
Jiang,S.,Ji,S.,Tang,Q.,Cui,X.,Yang,H.,Kan,B.,Gao,S.,2008b.Molecular character-ization of a novel adult diarrhoea rotavirus strain J19isolated in China and its signi?cance for the evolution and origin of group B rotaviruses.J.Gen.Virol.89 (October(Pt10)),2622–2629.
Jiang,X.,Jayaram,H.,Kumar,M.,Ludtke,S.J.,Estes,M.K.,Prasad,B.V.,2006.Cryoelec-tron microscopy structures of rotavirus NSP2–NSP5and NSP2–RNA complexes: implications for genome replication.J.Virol.80(November(21)),10829–10835. Joensuu,J.,Koskenniemi,E.,Pang,X.L.,Vesikari,T.,1997.Randomised placebo-controlled trial of rhesus-human reassortant rotavirus vaccine for prevention of severe rotavirus https://www.360docs.net/doc/c88711488.html,ncet350(October(9086)),1205–1209. Johansson,E.,Istrate,C.,Charpilienne,A.,Cohen,J.,Hinkula,J.,Poncet,D.,Svensson,L., Johansen,K.,2008.Amount of maternal rotavirus-speci?c antibodies in?uence the outcome of rotavirus vaccination of newborn mice with virus-like particles.
Vaccine26(February(6)),778–785.
Joosten,V.,Christien Lokman,C.,van den Hondel,C.,Punt,P.J.,2003.The production of antibody fragments and antibody fusion proteins by yeasts and?lamentous fungi.Microbial Cell Fact.2,1–5.
Kalica, A.R.,James Jr. A.D.,Kapikian, A.Z.,1978.Hemagglutination by simian rotavirus.J.Clin.Microbiol.7(3),314–315.
Kam,J.,Demmert,A.C.,Tanner,J.R.,McDonald,S.M.,Kelly,D.F.,2014.Sturctural dynamics of viral nanomachines.Technology2(1),1–5.
Kandasamy,S.,Chattha,K.S.,Vlasova,A.N.,Saif,L.J.,2014.Prenatal vitamin A de?-ciency impairs adaptive immune responses to pentavalent rotavirus vaccine (RotaTeq?)in a neonatal gnotobiotic pig model.Vaccine32(February(7)), 816–824.
92U.Desselberger/Virus Research190(2014)75–96
Kang,G.,2013.New-generation treatment?Targeted antiviral therapy for rotavirus.
Gastroenterology145(October(4)),711–714.
Kang,G.,Desai,R.,Arora,R.,Chitamabar,S.,Naik,T.N.,Krishnan,T.,Deshpande, J.,Gupte,M.D.,Venkatasubramaniam,S.,Gentsch,J.R.,Parashar,U.D.,Indian Rotavirus Strain Surveillance Network,Mathew, A.,Anita,S.r.,Ramani,S., Sowmynarayanan,T.V.,Moses,P.D.,Agarwal,I.,Simon,A.,Bose,A.,Arora,R., Chhabra,P.,Fadnis,P.,Bhatt,J.,Shetty,S.J.,Saxena,V.K.,Mathur,M.,Jadhav,A., Roy,S.,Mukherjee,A.,Singh,N.B.,2013.Diversity of circulating rotavirus strains in children hospitalized with diarrhea in India,2005–2009.Vaccine31(June
(27)),2879–2883.
Kapahnke,R.,Rappold,W.,Desselberger,U.,Riesner,D.,1986.The stiffness of dsRNA:hydrodynamic studies on?uorescence-labelled RNA segments of bovine rotavirus.Nucleic Acids Res.14(April(8)),3215–3228.
Kapikian,A.Z.,Hoshino,Y.,Chanock,R.M.,Perez-Schael,I.,1996.Jennerian and modi?ed Jennerian approach to vaccination against rotavirus diarrhea using a quadrivalent rhesus rotavirus(RRV)and human-RRV reassortant vaccine.Arch.
Virol.Suppl.12,163–175.
Kapusinszky,B.,Minor,P.,Delwart,E.,2012.Nearly constant shedding of diverse enteric viruses by two healthy infants.J.Clin.Microbiol.50(November(11)), 3427–3434.
Kelkar,S.D.,Zade,J.K.,2004.Group B rotaviruses similar to strain CAL-1,have been circulating in Western India since1993.Epidemiol.Infect.132(August(4)), 745–749.
Keswick,B.H.,Pickering,L.K.,DuPont,H.L.,Woodward,W.E.,1983.Survival and detection of rotaviruses on environmental surfaces in day care centers.Appl.
Environ.Microbiol.46(October(4)),813–816.
Kim,I.S.,Trask,S.D.,Babyonyshev,M.,Dormitzer,P.R.,Harrison,S.C.,2010.Effect of mutations in VP5hydrophobic loops on rotavirus cell entry.J.Virol.84(June
(12)),6200–6207.
Kindler,E.,Trojnar,E.,Heckel,G.,Otto,P.H.,Johne,R.,2013.Analysis of rotavirus species diversity and evolution including the newly determined full-length genome sequences of rotavirus F and G.Infect.Genet.Evol.14(March), 58–67.
Kobayashi,T.,Antar,A.A.,Boehme,K.W.,Danthi,P.,Eby,E.A.,Guglielmi,K.M.,Holm,
G.H.,Johnson,E.M.,Maginnis,M.S.,Naik,S.,Skelton,W.B.,Wetzel,J.D.,Wilson,
G.J.,Chappell,J.D.,Dermody,T.S.,2007.A plasmid-based reverse genetics sys-
tem for animal double-stranded RNA viruses.Cell Host Microbe1(April(2)), 147–157.
Kojima,K.,Taniguchi,K.,Kawagishi-Kobayashi,M.,Matsuno,S.,Urasawa,S.,2000.
Rearrangement generated in double genes,NSP1and NSP3,of viable progenies from a human rotavirus strain.Virus Res.67(April(2)),163–171.
Kojima,K.,Taniguchi,K.,Urasawa,T.,Urasawa,S.,1996.Sequence analysis of normal and rearranged NSP5genes from human rotavirus strains isolated in nature: implications for the occurrence of the rearrangement at the step of plus strand synthesis.Virology224(October(2)),446–452.
Komoto,S.,Sasaki,J.,Taniguchi,K.,2006.Reverse genetics system for introduction of site-speci?c mutations into the double-stranded RNA genome of infectious rotavirus.Proc.Natl.Acad.Sci.U.S.A.103(March(12)),4646–4651. Komoto,S.,Wakuda,M.,Ide,T.,Niimi,G.,Maeno,Y.,Higo-Moriguchi,K.,Taniguchi, K.,2011.Modi?cation of the trypsin cleavage site of rotavirus VP4to a furin-sensitive form does not enhance replication ef?ciency.J.Gen.Virol.92 (December(Pt12)),2914–2921.
Koo,H.L.,Neill,F.H.,Estes,M.K.,Munoz,F.M.,Cameron,A.,Dupont,H.L.,Atmar,R.L., 2013.Noroviruses:the most common pediatric viral enteric pathogen at a large university hospital after introduction of rotavirus vaccination.J.Pediatric Infect.
Dis.Soc.2(March(1)),57–60.
Kordasti,S.,Sj?vall,H.,Lundgren,O.,Svensson,L.,2004.Serotonin and vasoactive intestinal peptide antagonists attenuate rotavirus diarrhoea.Gut53(July(7)), 952–957.
La Frazia,S.,Ciucci,A.,Arnoldi,F.,Coira,M.,Gianferretti,P.,Angelini,M.,Belardo,
G.,Burrone,O.R.,Rossignol,J.F.,Santoro,M.G.,2013.Thiazolides,a new class of
antiviral agents effective against rotavirus infection,target viral morphogenesis, inhibiting viroplasm formation.J.Virol.87(October(20)),11096–11106. Lahon,A.,Maniya,N.H.,Tambe,G.U.,Chinchole,P.R.,Purwar,S.,Jacob,G.,Chitambar, S.D.,2013.Group B rotavirus infection in patients with acute gastroenteritis from India:1994–1995and2004–2010.Epidemiol.Infect.141(May(5)),969–975. Lappalainen,S.,Tamminen,K.,Vesikari,T.,Blazevic,V.,https://www.360docs.net/doc/c88711488.html,parative immuno-genicity in mice of rotavirus VP6tubular structures and virus-like particles.Hum.
Vaccin.Immunother.9(September(9)),1991–2001.
Lawton,J.A.,Estes,M.K.,Prasad,B.V.,1997.Three-dimensional visualization of mRNA release from actively transcribing rotavirus particles.Nat.Struct.Biol.
4(February(2)),118–121.
Le Pendu,J.,Nystroem,K.,Ruvoen-Clouet,N.,2014.Host-pathogen co-evolution and glycan interactions.Curr.Opin.Virol.7C(Jul(4)),88–94.
Leshem,E.,Moritz,R.E.,Curns,A.T.,Zhou,F.,Tate,J.E.,Lopman,B.A.,Parashar,U.D., 2014.Rotavirus vaccines and health care utilization for diarrhea in the United States(2007-2011).Pediatrics(June),pii:peds.2013-3849(Epub ahead of print). Li,W.,Manktelow,E.,von Kirchbach,J.C.,Gog,J.R.,Desselberger,U.,Lever,A.M., 2010.Genomic analysis of codon,sequence and structural conservation with selective biochemical-structure mapping reveals highly conserved and dynamic structures in rotavirus RNAs with potential cis-acting functions.Nucleic Acids Res.38(November(21)),7718–7735.
Libonati,M.H.,Dennis,A.F.,Ramani,S.,McDonald,S.M.,Akopov,A.,Kirkness,E.F., Kang,G.,Patton,J.T.,2014.Absence of genetic differences among G10P[11] rotaviruses associated with asymptomatic and symptomatic neonatal infections in Vellore,India.J.Virol.(June),pii:JVI.01417-14(Epub ahead of print).Liu,F.,Li,G.,Wen,K.,Wu,S.,Zhang,Y.,Bui,T.,Yang,X.,Kocher,J.,Sun,J.,Jortner,B., Yuan,L.,https://www.360docs.net/doc/c88711488.html,ctobacillus rhamnosus GG on rotavirus-induced injury of ileal epithelium in gnotobiotic pigs.J.Pediatr.Gastroenterol.Nutr.57(December(6)), 750–758.
Liu,J.,Kibiki,G.,Maro,V.,Maro,A.,Kumburu,H.,Swai,N.,Taniuchi,M.,Gratz,J., Toney,D.,Kang,G.,Houpt,E.,2011.Multiplex reverse transcription PCR Luminex assay for detection and quantitation of viral agents of gastroenteritis.J.Clin.
Virol.50(April(4)),308–313.
Liu,L.,Johnson,H.L.,Cousens,S.,Perin,J.,Scott,S.,Lawn,J.E.,Rudan,I.,Campbell,H., Cibulskis,R.,Li,M.,Mathers,C.,Black,R.E.,Child Health Epidemiology Reference Group of WHO and UNICEF,2012.Global,regional,and national causes of child mortality:an updated systematic analysis for2010with time trends since2000.
Lancet379(June(9832)),2151–2161.
López,S.,Arias,C.F.,2004.Multistep entry of rotavirus into cells:a Versaillesque dance.Trends Microbiol.12(June(6)),271–278.
López,T.,Silva-Ayala,D.,López,S.,Arias,C.F.,2011.Replication of the rotavirus genome requires an active ubiquitin-proteasome system.J.Virol.85(November
(22)),11964–11971.
Lopman,B.A.,Pitzer,V.E.,Sarkar,R.,Gladstone,B.,Patel,M.,Glasser,J.,Gambhir,M., Atchison,C.,Grenfell,B.T.,Edmunds,W.J.,Kang,G.,Parashar,U.D.,2012.Under-standing reduced rotavirus vaccine ef?cacy in low socio-economic settings.PLoS ONE7(8),e41720.
Lu,X.,McDonald,S.M.,Tortorici,M.A.,Tao,Y.J.,Vasquez-Del Carpio,R.,Nibert,M.L., Patton,J.T.,Harrison,S.C.,2008.Mechanism for coordinated RNA packaging and genome replication by rotavirus polymerase VP1.Structure16(November(11)), 1678–1688.
Luchs,A.,Timenetsky,M.doC.,2014.G8P[6]rotaviruses isolated from Amerindian children in Mato Grosso do Sul,Brazil,during2009:close relationship of the G and P genes with those of bovine and bat strains.J.Gen.Virol.95(March(Pt3)), 627–641.
Ludert,J.E.,Michelangeli,F.,Gil,F.,Liprandi,F.,Esparza,J.,1987.Penetration and uncoating of rotaviruses in cultured cells.Intervirology27(2),95–101. Lundgren,O.,Peregrin,A.T.,Persson,K.,Kordasti,S.,Uhnoo,I.,Svensson,L.,2000.Role of the enteric nervous system in the?uid and electrolyte secretion of rotavirus diarrhea.Science287(January(5452)),491–495.
Mackow,E.R.,Barnett,J.W.,Chan,H.,Greenberg,H.B.,1989.The rhesus rotavirus outer capsid protein VP4functions as a hemagglutinin and is antigenically con-served when expressed by a baculovirus recombinant.J.Virol.63(April(4)), 1661–1668.
Madhi,S.A.,Cunliffe,N.A.,Steele,D.,Witte,D.,Kirsten,M.,Louw,C.,Ngwira,B., Victor,J.C.,Gillard,P.H.,Cheuvart,B.B.,Han,H.H.,Neuzil,K.M.,2010.Effect of human rotavirus vaccine on severe diarrhea in African infants.N.Engl.J.Med.
362(January(4)),289–298.
Maes,P.,Matthijnssens,J.,Rahman,M.,Van Ranst,M.,2009.RotaC:a web-based tool for the complete genome classi?cation of group A rotaviruses.BMC Microbiol.
9(November),238.
Malek,M.A.,Curns,A.T.,Holman,R.C.,Fischer,T.K.,Bresee,J.S.,Glass,R.I.,Steiner,C.A., Parashar,U.D.,2006.Diarrhea-and rotavirus-associated hospitalizations among children less than5years of age:United States,1997and2000.Pediatrics117 (June(6)),1887–1892.
Malherbe,H.,Harwin,R.,1963.The cytopathic effects of vervet monkey viruses.S.
Afr.Med.J.37(April),407–411.
Martella,V.,Bányai,K.,Matthijnssens,J.,Buonavoglia,C.,Ciarlet,M.,2010.Zoonotic aspects of rotaviruses.Vet.Microbiol.140(January(3–4)),246–255. Marthaler,D.,Rossow,K.,Culhane,M.,Collins,J.,Goyal,S.,Ciarlet,M.,Matthijnssens, J.,2013.Identi?cation,phylogenetic analysis and classi?cation of porcine group
C rotavirus VP7sequences from the United States and Canada.Virology446
(November(1–2)),189–198.
Marthaler,D.,Rossow,K.,Culhane,M.,Goyal,S.,Collins,J.,Matthijnssens,J.,Nelson, M.,Ciarlet,M.,2014.Widespread rotavirus H in commercially raised pigs,United States.Emerg.Infect.Dis.20(7),1203–1206.
Marthaler,D.,Rossow,K.,Gramer,M.,Collins,J.,Goyal,S.,Tsunemitsu,H.,Kuga,K., Suzuki,T.,Ciarlet,M.,Matthijnssens,J.,2012.Detection of substantial porcine group B rotavirus genetic diversity in the United States,resulting in a mod-i?ed classi?cation proposal for G genotypes.Virology433(November(1)), 85–96.
Martin,D.,Duarte,M.,Lepault,J.,Poncet,D.,2010.Sequestration of free tubulin molecules by the viral protein NSP2induces microtubule depolymerization during rotavirus infection.J.Virol.84(March(5)),2522–2532.
Martínez-Laso,J.,Román, A.,Rodriguez,M.,Cervera,I.,Head,J.,Rodríguez-Avial,I.,Picazo,J.J.,2009.Diversity of the G3genes of human rotaviruses in isolates from Spain from2004to2006:cross-species transmission and inter-genotype recombination generated alleles.J.Gen.Virol.90(April(Pt4)), 935–943.
Mathieu,M.,Petitpas,I.,Navaza,J.,Lepault,J.,Kohli,E.,Pothier,P.,Prasad,B.V., Cohen,J.,Rey,F.A.,2001.Atomic structure of the major capsid protein of rotavirus:implications for the architecture of the virion.EMBO J.20(April(7)), 1485–1497.
Matson,D.O.,2006.RotaShield:the ill-fated rhesus-human reassortant rotavirus vaccine.Pediatr.Ann.35(January(1)),44–50.
Matsui,S.M.,Of?t,P.A.,Vo,P.T.,Mackow,E.R.,Ben?eld,D.A.,Shaw,R.D.,Padilla-Noriega,L.,Greenberg,H.B.,1989a.Passive protection against rotavirus-induced diarrhea by monoclonal antibodies to the heterotypic neutralization domain of VP7and the VP8fragment of VP4.J.Clin.Microbiol.27(4),780–782.
Matsui,S.M.,Mackow, E.R.,Greenberg,H.B.,1989b.Molecular determinant of rotavirus neutralization and protection.Adv.Virus Res.36,181–214.
U.Desselberger/Virus Research190(2014)75–9693
Matsuo,E.,Roy,P.,2009.Bluetongue virus VP6acts early in the replication cycle and can form the basis of chimeric virus formation.J.Virol.83(September(17)), 8842–8848.
Matthijnssens,J.,Ciarlet,M.,Heiman,E.,Arijs,I.,Delbeke,T.,McDonald,S.M., Palombo,E.A.,Iturriza-Gómara,M.,Maes,P.,Patton,J.T.,Rahman,M.,Van Ranst, M.,2008a.Full genome-based classi?cation of rotaviruses reveals a common ori-gin between human Wa-Like and porcine rotavirus strains and human DS-1-like and bovine rotavirus strains.J.Virol.82(April(7)),3204–3219. Matthijnssens,J.,Ciarlet,M.,McDonald,S.M.,Attoui,H.,Bányai,K.,Brister,J.R.,Buesa, J.,Esona,M.D.,Estes,M.K.,Gentsch,J.R.,Iturriza-Gómara,M.,Johne,R.,Kirkwood,
C.D.,Martella,V.,Mertens,P.P.,Nakagomi,O.,Parre?no,V.,Rahman,M.,Ruggeri,
F.M.,Saif,L.J.,Santos,N.,Steyer,A.,Taniguchi,K.,Patton,J.T.,Desselberger,U.,
Van Ranst,M.,2011a.Uniformity of rotavirus strain nomenclature proposed by the Rotavirus Classi?cation Working Group(RCWG).Arch.Virol156(August
(8)),1397–1413.
Matthijnssens,J.,Ciarlet,M.,Rahman,M.,Attoui,H.,Bányai,K.,Estes,M.K.,Gentsch, J.R.,Iturriza-Gómara,M.,Kirkwood,C.D.,Martella,V.,Mertens,P.P.,Nakagomi, O.,Patton,J.T.,Ruggeri,F.M.,Saif,L.J.,Santos,N.,Steyer,A.,Taniguchi,K.,Des-selberger,U.,Van Ranst,M.,2008b.Recommendations for the classi?cation of group A rotaviruses using all11genomic RNA segments.Arch.Virol153(8), 1621–1629.
Matthijnssens,J.,De Grazia,S.,Piessens,J.,Heylen,E.,Zeller,M.,Giammanco,G.M., Bányai,K.,Buonavoglia,C.,Ciarlet,M.,Martella,V.,Van Ranst,M.,2011b.Multiple reassortment and interspecies transmission events contribute to the diversity of feline,canine and feline/canine-like human group A rotavirus strains.Infect.
Genet.Evol.11(August(6)),1396–1406.
Matthijnssens,J.,Otto,P.H.,Ciarlet,M.,Desselberger,U.,Van Ranst,M.,Johne,R., 2012.VP6-sequence-based cutoff values as a criterion for rotavirus species demarcation.Arch.Virol157(June(6)),1177–1182.
Matthijnssens,J.,Van Ranst,M.,2012.Genotype constellation and evolution of group A rotaviruses infecting humans.Curr.Opin.Virol.2(August(4)), 426–433.
Matthijnssens,J.,Zeller,M.,Heylen, E.,De Coster,S.,Vercauteren,J.,Braeck-man,T.,Van Herck,K.,Meyer,N.,Pirc?on,J.Y.,Soriano-Gabarro,M.,Azou,M., Capiau,H.,De Koster,J.,Maernoudt,A.S.,Raes,M.,Verdonck,L.,Verghote, M.,Vergison, A.,Van Damme,P.,Van Ranst,M.,2014.The RotaBel study group,Higher proportion of G2P[4]rotaviruses in vaccinated hospitalised cases compared to unvaccinated hospitalised cases,despite high vaccine effec-tiveness against heterotypic G2P[4]rotaviruses.Clin.Microbiol.Infect.(Mar), https://www.360docs.net/doc/c88711488.html,/10.1111/1469-0691.12612(Epub ahead of print).
McClain,B.,Settembre,E.,Temple,B.R.,Bellamy,A.R.,Harrison,S.C.,2010.X-ray crystal structure of the rotavirus inner capsid particle at3.8?A resolution.J.Mol.
Biol.397(March(2)),587–599.
McClenahan,S.D.,Krause,P.R.,Uhlenhaut,C.,2011.Molecular and infectivity studies of porcine circovirus in vaccines.Vaccine29(June(29–30)),4745–4753. McIntyre,M.,Rosenbaum,V.,Rappold,W.,Desselberger,M.,Wood,D.,Desselberger, U.,1987.Biophysical characterization of rotavirus particles containing rear-ranged genomes.J.Gen.Virol.68(November(Pt11)),2961–2966.
McNulty,M.S.,Curran,W.L.,McFerran,J.B.,1976.The morphogenesis of a cytopathic bovine rotavirus in Madin-Darby bovine kidney cells.J.Gen.Virol.33(December
(3)),503–508.
Mebus,C.A.,Underdahl,N.R.,Rhodes,M.B.,Twiehaus,M.J.,1969.Further studies on neonatal calf diarrhea virus.Proc.Annu.Meet.U.S.Anim.Health Assoc.73, 97–99.
Minot,S.,Bryson,A.,Chehoud,C.,Wu,G.D.,Lewis,J.D.,Bushman,F.D.,2013.Rapid evolution of the human gut virome.Proc.Natl.Acad.Sci.U.S.A.110(July(30)), 12450–12455.
Minot,S.,Grunberg,S.,Wu,G.D.,Lewis,J.D.,Bushman,F.D.,2012.Hypervariable loci in the human gut virome.Proc.Natl.Acad.Sci.U.S.A.109(March(10)), 3962–3966.
Mohanty,S.K.,Donnelly,B.,Bondoc,A.,Jafri,M.,Walther,A.,Coots,A.,McNeal,M., Witte,D.,Tiao,G.M.,2013.Rotavirus replication in the cholangiocyte medi-ates the temporal dependence of murine biliary atresia.PLoS ONE8(July(7)), e69069.
Molinari,B.L.,Lorenzetti,E.,Otonel,R.A.,Al?eri,A.F.,Al?eri,A.A.,2014.Species h rotavirus detected in piglets with diarrhea,Brazil,2012.Emerg.Infect.Dis.20 (June(6)),1019–1022.
Montero,H.,Arias,C.F.,Lopez,S.,2006.Rotavirus nonstructural protein NSP3is not required for viral protein synthesis.J.Virol.80(September(18)),9031–9038. Mrukowicz,J.Z.,Wetzel,J.D.,Goral,M.I.,Fogo,A.B.,Wright,P.F.,Dermody,T.S.,1998.
Viruses and cells with mutations affecting viral entry are selected during per-sistent rotavirus infections of MA104cells.J.Virol.72(April(4)),3088–3097. Mullick,S.,Mukherjee,A.,Ghosh,S.,Pazhani,G.P.,Sur,D.,Manna,B.,Nataro,J.P., Levine,M.M.,Ramamurthy,T.,Chawla-Sarkar,M.,2013.Genomic analysis of human rotavirus strains G6P[14]and G11P[25]isolated from Kolkata in2009 reveals interspecies transmission and complex reassortment events.Infect.
Genet.Evol.14(March),15–21.
Murphy,B.R.,Morens,D.M.,Simonsen,L.,Chanock,R.M.,La Montagne,J.R.,Kapikian,
A.Z.,2003a.Reappraisal of the association of intussusception with the licensed
live rotavirus vaccine challenges initial conclusions.J.Infect.Dis.187(April(8)), 1301–1308.
Murphy,T.V.,Gargiullo,P.M.,Massoudi,M.S.,Nelson,D.B.,Jumaan,A.O.,Okoro,
C.A.,Zanardi,L.R.,Setia,S.,Fair,E.,LeBaron,C.W.,Wharton,M.,Livengood,J.R.,
Rotavirus Intussusception Investigation Team,2001.Intussusception among infants given an oral rotavirus vaccine.N.Engl.J.Med.344(February(8)), 564–572.Murphy,T.V.,Smith,P.J.,Gargiullo,P.M.,Schwartz,B.,2003b.The?rst rotavirus vac-cine and intussusception:epidemiological studies and policy decisions.J.Infect.
Dis.187(April(8)),1309–1313.
Mwenda,J.M.,Ntoto,K.M.,Abebe,A.,Enweronu-Laryea,C.,Amina,I.,Mchomvu,J., Kisakye,A.,Mpabalwani,E.M.,Pazvakavambwa,I.,Armah,G.E.,Seheri,L.M.,Kiu-lia,N.M.,Page,N.,Widdowson,M.A.,Steele,A.D.,2010.Burden and epidemiology of rotavirus diarrhea in selected African countries:preliminary results from the African Rotavirus Surveillance Network.J.Infect.Dis.202(September(Suppl.)), S5–S11.
Nandi,S.,Chanda,S.,Bagchi,P.,Nayak,M.K.,Bhowmick,R.,Chawla-Sarkar,M.,2014.
MAVS protein is attenuated by rotavirus nonstructural protein1.PLoS ONE9 (March(3)),e92126.
Navarro,A.,Trask,S.D.,Patton,J.T.,2013.Generation of genetically stable recom-binant rotaviruses containing novel genome rearrangements and heterologous sequences by reverse genetics.J.Virol.87(June(11)),6211–6220. Nejmeddine,M.,Trugnan,G.,Sapin,C.,Kohli,E.,Svensson,L.,Lopez,S.,Cohen,J., 2000.Rotavirus spike protein VP4is present at the plasma membrane and is associated with microtubules in infected cells.J.Virol.74(April(7)),3313–3320. Newton,K.,Meyer,J.C.,Bellamy,A.R.,Taylor,J.A.,1997.Rotavirus nonstructural gly-coprotein NSP4alters plasma membrane permeability in mammalian cells.J.
Virol.71(December(12)),9458–9465.
Nilsson,M.,Svenungsson,B.,Hedlund,K.O.,Uhnoo,I.,Lagergren,A.,Akre,T.,Svens-son,L.,2000.Incidence and genetic diversity of group C rotavirus among adults.
J.Infect.Dis.182(September(3)),678–684.
Of?t,P.A.,1994.Rotaviruses:immunological determinants of protection against infection and disease.Adv.Virus Res.44,161–202.
Of?t,P.A.,Clark,H.F.,Blavat,G.,Greenberg,H.B.,1986a.Reassortant rotaviruses containing structural proteins vp3and vp7from different parents induce anti-bodies protective against each parental serotype.J.Virol.60(November(2)), 491–496.
Of?t,P.A.,Shaw,R.D.,Greenberg,H.B.,1986b.Passive protection against rotavirus-induced diarrhea by monoclonal antibodies to surface proteins vp3and vp7.J.
Virol.58(May(2)),700–703.
O’Neal,C.M.,Crawford,S.E.,Estes,M.K.,Conner,M.E.,1997.Rotavirus virus-like particles administered mucosally induce protective immunity.J.Virol.71 (November(11)),8707–8717.
O’Neal,C.M.,Harriman,G.R.,Conner,M.E.,2000.Protection of the villus epithe-lial cells of the small intestine from rotavirus infection does not require immunoglobulin A.J.Virol.74(May(9)),4102–4109.
O’Neill,H.G.,Mlera,L.,Wentzel,J.,van Dijk,A.A.,2013.Rotavirus transcripts activate protein kinase R,are sensed by RIG-I and induce IFN-gamma,IFN lambda-1and CXCL10in HEK293H cells.In:5th European Rotavirus Biology Meeting,Valencia, October2013,p.19,Abstract book O-03.
Osborne,M.P.,Haddon,S.J.,Worton,K.J.,Spencer,A.J.,Starkey,W.G.,Thornber,D., Stephen,J.,1991.Rotavirus-induced changes in the microcirculation of intestinal villi of neonatal mice in relation to the induction and persistence of diarrhea.J.
Pediatr.Gastroenterol.Nutr.12(January(1)),111–120.
Otto,P.H.,Ahmed,M.U.,Hotzel,H.,Machnowska,P.,Reetz,J.,Roth,B.,Trojnar,E., Johne,R.,2012.Detection of avian rotaviruses of groups A,D,F and G in diseased chickens and turkeys from Europe and Bangladesh.Vet.Microbiol.156(April (1–2)),8–15.
Papp,H.,Borzák,R.,Farkas,S.,Kisfali,P.,Lengyel,G.,Molnár,P.,Melegh,B.,Matthi-jnssens,J.,Jakab,F.,Martella,V.,Bányai,K.,2013.Zoonotic transmission of reassortant porcine G4P[6]rotaviruses in Hungarian pediatric patients identi-?ed sporadically over a15year period.Infect.Genet.Evol.19(October),71–80. Parashar,U.D.,Burton,A.,Lanata,C.,Boschi-Pinto,C.,Shibuya,K.,Steele,D.,Birming-ham,M.,Glass,R.I.,2009.Global mortality associated with rotavirus disease among children in2004.J.Infect.Dis.200(November(Suppl.1)),S9–S15. Parashar,U.D.,Gibson,C.J.,Bresee,J.S.,Glass,R.I.,2006.Rotavirus and severe child-hood diarrhea.Emerg.Infect.Dis.12(February(2)),304–306.
Parashar,U.D.,Orenstein,W.A.,2013.Editorial commentary:intussusception and rotavirus vaccination–balancing risk against bene?t.Clin.Infect.Dis.57 (November(10)),1435–1437.
Parra,G.I.,Bok,K.,Martínez,M.,Gomez,J.A.,2004.Evidence of rotavirus intragenic recombination between two sublineages of the same genotype.J.Gen.Virol.85 (June(Pt6)),1713–1716.
Parra,M.,Herrera,D.,Calvo-Calle,J.M.,Stern,L.J.,Parra-López,C.A.,Butcher,E., Franco,M.,Angel,J.,2014.Circulating human rotavirus speci?c CD4T cells iden-ti?ed with a class II tetramer express the intestinal homing receptors?4?7and CCR9.Virology452–453(March),191–201.
Pastor, A.R.,Rodríguez-Limas,W.A.,Contreras,M.A.,Esquivel, E.,Esquivel-Guadarrama,F.,Ramírez,O.T.,Palomares,L.A.,2014.The assembly conformation of rotavirus VP6determines its protective ef?cacy against rotavirus challenge in mice.Vaccine32(May(24)),2874–2877.
Patel,M.,Glass,R.I.,Jiang,B.,Santosham,M.,Lopman,B.,Parashar,U.,2013.A sys-tematic review of anti-rotavirus serum IgA antibody titer as a potential correlate of rotavirus vaccine ef?cacy.J.Infect.Dis.208(July(2)),284–294.
Patel,M.M.,López-Collada,V.R.,Bulh?es,M.M.,De Oliveira,L.H.,Bautista Márquez,
A.,Flannery,
B.,Esparza-Aguilar,M.,Montenegro Renoiner, E.I.,Luna-Cruz,
M.E.,Sato,H.K.,Hernández-Hernández Ldel, C.,Toledo-Cortina,G.,Cerón-Rodríguez,M.,Osnaya-Romero,N.,Martínez-Alcazar,M.,Aguinaga-Villasenor, R.G.,Plascencia-Hernández,A.,Fojaco-González,F.,Hernández-Peredo Rezk,
G.,Gutierrez-Ramírez,S.F.,Dorame-Castillo,R.,Tinajero-Pizano,R.,Mercado-
Villegas,B.,Barbosa,M.R.,Maluf,E.M.,Ferreira,L.B.,de Carvalho,F.M.,dos Santos,
A.R.,Cesar,E.D.,de Oliveira,M.E.,Silva,C.L.,de Los Angeles Cortes,M.,Ruiz Matus,
C.,Tate,J.,Gargiullo,P.,Parashar,U.
D.,2011.Intussusception risk and health
94U.Desselberger/Virus Research190(2014)75–96
bene?ts of rotavirus vaccination in Mexico and Brazil.N.Engl.J.Med.364(June
(24)),2283–2292.
Patel,M.M.,Parashar,U.D.,2009.Assessing the effectiveness and public health impact of rotavirus vaccines after introduction in immunization programs.J.
Infect.Dis.200(November(Suppl.1)),S291–S299.
Patel,N.C.,Hertel,P.M.,Estes,M.K.,de la Morena,M.,Petru,A.M.,Noroski,L.M.,Revell, P.A.,Hanson,I.C.,Paul,M.E.,Rosenblatt,H.M.,Abramson,S.L.,2010.Vaccine-acquired rotavirus in infants with severe combined immunode?ciency.N.Engl.
J.Med.362(January(4)),314–319.
Payne,D.C.,Boom,J.A.,Staat,M.A.,Edwards,K.M.,Szilagyi,P.G.,Klein,E.J.,Sel-varangan,R.,Azimi,P.H.,Harrison, C.,Moffatt,M.,Johnston,S.H.,Sahni, L.C.,Baker,C.J.,Rench,M.A.,Donauer,S.,McNeal,M.,Chappell,J.,Weinberg,
G.A.,Tasslimi,A.,Tate,J.E.,Wikswo,M.,Curns,A.T.,Sulemana,I.,Mijatovic-
Rustempasic,S.,Esona,M.D.,Bowen,M.D.,Gentsch,J.R.,Parashar,U.D.,2013a.
Effectiveness of pentavalent and monovalent rotavirus vaccines in concurrent use among US children<5years of age,2009–2011.Clin.Infect.Dis.57(July(1)), 13–20.
Payne,D.C.,Vinjé,J.,Szilagyi,P.G.,Edwards,K.M.,Staat,M.A.,Weinberg,G.A.,Hall,
C.B.,Chappell,J.,Bernstein,
D.I.,Curns,A.T.,Wikswo,M.,Shirley,S.H.,Hall,A.J.,
Lopman,B.,Parashar,U.D.,2013b.Norovirus and medically attended gastroen-teritis in U.S.children.N.Engl.J.Med.368(March(12)),1121–1130.
Pedley,S.,Hundley,F.,Chrystie,I.,McCrae,M.A.,Desselberger,U.,1984.The genomes of rotaviruses isolated from chronically infected immunode?cient children.J.
Gen.Virol.65(July(Pt7)),1141–1150.
Peláez-Carvajal,D.,Cotes-Cantillo,K.,Paternina-Caicedo,A.,Gentsch,J.,de la Hoz-Restrepo,F.,Patel,M.,2014.Characterization of rotavirus genotypes before and after the introduction of a monovalent rotavirus vaccine in Colombia.J.Med.
Virol.86(June(6)),1083–1086.
Pérez-Schael,I.,Gunti?nas,M.J.,Pérez,M.,Pagone,V.,Rojas,A.M.,González,R.,Cunto, W.,Hoshino,Y.,Kapikian,A.Z.,1997.Ef?cacy of the rhesus rotavirus-based quadrivalent vaccine in infants and young children in Venezuela.N.Engl.J.Med.
337(October(17)),1181–1187.
Pérez-Vargas,J.,Romero,P.,López,S.,Arias,C.F.,2006.The peptide-binding and ATPase domains of recombinant hsc70are required to interact with rotavirus and reduce its infectivity.J.Virol.80(April(7)),3322–3331.
Periz,J.,Celma,C.,Jing,B.,Pinkney,J.N.,Roy,P.,Kapanidis,A.N.,2013.Rotavirus mRNAS are released by transcript-speci?c channels in the double-layered viral capsid.Proc.Natl.Acad.Sci.U.S.A.110(July(29)),12042–12047.
Peter,G.,Myers,M.G.,National Vaccine Advisory Committee;National Vaccine Pro-gram Of?ce,2002.Intussusception,rotavirus,and oral vaccines:summary of a workshop.Pediatrics110(December(6)),e67.
Phan,T.G.,Okitsu,S.,Maneekarn,N.,Ushijima,H.,2007.Evidence of intra-genic recombination in G1rotavirus VP7genes.J.Virol.81(September(18)), 10188–10194.
Phan,T.G.,Vo,N.P.,Bonkoungou,I.J.,Kapoor,A.,Barro,N.,O’Ryan,M.,Kapusin-szky,B.,Wang,C.,Delwart,E.,2012.Acute diarrhea in West African children: diverse enteric viruses and a novel parvovirus genus.J.Virol.86(October(20)), 11024–11030.
Pickering,L.K.,Bartlett,A.V.,3rd,Reves,R.R.,Morrow,A.,1988.Asymptomatic excre-tion of rotavirus before and after rotavirus diarrhea in children in day care centers.J.Pediatr.112(March(3)),361–365.
Piron,M.,Delaunay,T.,Grosclaude,J.,Poncet,D.,1999.Identi?cation of the RNA-binding,dimerization,and eIF4GI-binding domains of rotavirus nonstructural protein NSP3.J.Virol.73(July(7)),5411–5421.
Piron,M.,Vende,P.,Cohen,J.,Poncet,D.,1998.Rotavirus RNA-binding protein NSP3 interacts with eIF4GI and evicts the poly(A)binding protein from eIF4F.EMBO J.17(October(19)),5811–5821.
Pizarro,D.,Posada,G.,Sandi,L.,Moran,J.R.,1991.Rice-based oral electrolyte solu-tions for the management of infantile diarrhea.N.Engl.J.Med.324(February
(8)),517–521,Erratum in:N.Engl.J.Med.1992,326(February(7)),488–489. Prasad,B.V.,Rothnagel,R.,Zeng,C.Q.,Jakana,J.,Lawton,J.A.,Chiu,W.,Estes,M.K., 1996.Visualization of ordered genomic RNA and localization of transcriptional complexes in rotavirus.Nature382(August(6590)),471–473.
Qin,L.,Ren,L.,Zhou,Z.,Lei,X.,Chen,L.,Xue,Q.,Liu,X.,Wang,J.,Hung,T.,2011.
Rotavirus nonstructural protein1antagonizes innate immune response by inter-acting with retinoic acid inducible gene I.Virol.J.8(December),526. Quintanar-Solares,M.,Yen,C.,Richardson,V.,Esparza-Aguilar,M.,Parashar,U.D., Patel,M.M.,2011.Impact of rotavirus vaccination on diarrhea-related hospi-talizations among children<5years of age in Mexico.Pediatr.Infect.Dis.J.30 (January(1Suppl.)),S11–S15.
Ramani,S.,Cortes-Pen?eld,N.W.,Hu,L.,Crawford,S.E.,Czako,R.,Smith,D.F.,Kang,
G.,Ramig,R.F.,Le Pendu,J.,Prasad,B.V.,Estes,M.K.,2013.The VP8*domain of
neonatal rotavirus strain G10P[11]binds to type II precursor glycans.J.Virol.87 (July(13)),7255–7264.
Ramani,S.,Paul, A.,Saravanabavan, A.,Menon,V.K.,Arumugam,R.,Sowmya-narayanan,T.V.,Samuel,P.,Kang,G.,2010.Rotavirus antigenemia in Indian children with rotavirus gastroenteritis and asymptomatic infections.Clin.Infect.
Dis.51(December(11)),1284–1289.
Ramig,R.F.,2007.Systemic rotavirus infection.Expert Rev.Anti Infect.Ther.5 (August(4)),591–612.
Ramig,R.F.,2004.Pathogenesis of intestinal and systemic rotavirus infection.J.Virol.
78(October(19)),10213–10220.
Ray,P.G.,Kelkar,S.D.,Walimbe,A.M.,Biniwale,V.,Mehendale,S.,2007.Rotavirus immunoglobulin levels among Indian mothers of two socio-economic groups and occurrence of rotavirus infections among their infants up to six months.J.
Med.Virol.79(March(3)),341–349.Rha,B.,Tate,J.E.,Payne,D.C.,Cortese,M.M.,Lopman,B.A.,Curns,A.T.,Parashar, U.D.,2014.Effectiveness and impact of rotavirus vaccines in the United States–2006–2012.Expert Rev.Vaccines13(March(3)),365–376.
Richards,J.E.,Desselberger,U.,Lever,A.M.,2013.Experimental pathways towards developing a rotavirus reverse genetics system:synthetic full length rotavirus ssRNAs are neither infectious nor translated in permissive cells.PLoS ONE8 (September(9)),e74328.
Richardson,S.,Grimwood,K.,Gorrell,R.,Palombo,E.,Barnes,G.,Bishop,R.,1998.
Extended excretion of rotavirus after severe diarrhoea in young https://www.360docs.net/doc/c88711488.html,ncet 351(June(9119)),1844–1848.
Richardson,V.,Hernandez-Pichardo,J.,Quintanar-Solares,M.,Esparza-Aguilar,M., Johnson,B.,Gomez-Altamirano,C.M.,Parashar,U.,Patel,M.,2010.Effect of rotavirus vaccination on death from childhood diarrhea in Mexico.N.Engl.J.
Med.362(January(4)),299–305.
Riepenhoff-Talty,M.,Dharakul,T.,Kowalski,E.,Michalak,S.,Ogra,P.L.,1987.Per-sistent rotavirus infection in mice with severe combined immunode?ciency.J.
Virol.61(October(10)),3345–3348.
Rodríguez,J.M.,Chichón,F.J.,Martín-Forero,E.,González-Camacho,F.,Carrascosa, J.L.,Castón,J.R.,Luque,D.,2014.New insights into rotavirus entry machinery: stabilization of rotavirus spike conformation is independent of trypsin cleavage.
PLoS Pathog.10(May(5)),e1004157.
Rodríguez,M.,Wood,C.,Sanchez-López,R.,Castro-Acosta,R.M.,Ramírez,O.T.,Palo-mares,L.A.,2013.Understanding internalization of rotavirus VP6nanotubes by cells:towards a recombinant vaccine.Arch.Virol.(November)(Epub ahead of print).
Rodríguez-Limas,W.A.,Pastor, A.R.,Esquivel-Soto, E.,Esquivel-Guadarrama, F., Ramírez,O.T.,Palomares,L.A.,2014.Immunogenicity and protective ef?cacy of yeast extracts containing rotavirus-like particles:a potential veterinary vaccine.
Vaccine32(May(24)),2794–2798.
Rojas,O.L.,González,A.M.,González,R.,Pérez-Schael,I.,Greenberg,H.B.,Franco, M.A.,Angel,J.,2003.Human rotavirus speci?c T cells:quanti?cation by ELISPOT and expression of homing receptors on CD4+T cells.Virology314(September
(2)),671–679.
Rojas,O.L.,Narváez,C.F.,Greenberg,H.B.,Angel,J.,Franco,M.A.,2008.Characteri-zation of rotavirus speci?c B cells and their relation with serological memory.
Virology380(October(2)),234–242.
Rossignol,J.F.,Abu-Zekry,M.,Hussein,A.,Santoro,M.G.,2006.Effect of nitazoxanide for treatment of severe rotavirus diarrhoea:randomised double-blind placebo-controlled https://www.360docs.net/doc/c88711488.html,ncet368(July(9530)),124–129.
Rotavirus Classi?cation Working Group,6th meeting,Valencia,October2013. Rubio,R.M.,Mora,S.I.,Romero,P.,Arias,C.F.,López,S.,2013.Rotavirus prevents the expression of host responses by blocking the nucleocytoplasmic transport of polyadenylated mRNAs.J.Virol.87(June(11)),6336–6345.
Ruiz-Palacios,G.M.,Pérez-Schael,I.,Velázquez,F.R.,Abate,H.,Breuer,T.,Clemens, S.C.,Cheuvart,B.,Espinoza,F.,Gillard,P.,Innis,B.L.,Cervantes,Y.,Linhares,A.C., López,P.,Macías-Parra,M.,Ortega-Barría,E.,Richardson,V.,Rivera-Medina,
D.M.,Rivera,L.,Salinas,B.,Pavía-Ruz,N.,Salmerón,J.,Rüttimann,R.,Tinoco,
J.C.,Rubio,P.,Nu?nez,E.,Guerrero,M.L.,Yarzábal,J.P.,Damaso,S.,Tornieporth, N.,Sáez-Llorens,X.,Vergara,R.F.,Vesikari,T.,Bouckenooghe,A.,Clemens,R.,De Vos,B.,O’Ryan,M.,Human Rotavirus Vaccine Study Group,2006.Safety and ef?-cacy of an attenuated vaccine against severe rotavirus gastroenteritis.N.Engl.J.
Med.354(January(1)),11–22.
Ryan,E.T.,2013.The intestinal pathobiome:its reality and consequences among infants and young children in resource-limited settings.J.Infect.Dis.208 (December(11)),1732–1733.
Sachsenroder,J.,Twardziok,S.,Hammerl,J.A.,Janczyk,P.,Wrede,P.,Hertwig,S., Johne,R.,2012.Simultaneous identi?cation of DNA and RNA viruses present in pig faeces using process-controlled deep sequencing.PLoS ONE7,e34631. SAGE,2009.Meeting of the Immunization Strategic Advisory Group of Experts, April2009–conclusions and recommendations.Wkly.Epidem.Rec.84, 220–235.
Salazar-Lindo, E.,Santisteban-Ponce,J.,Chea-Woo, E.,Gutierrez,M.,2000.
Racecadotril in the treatment of acute watery diarrhea in children.N.Engl.J.
Med.343(August(7)),463–467.
Sánchez-San Martín,C.,López,T.,Arias,C.F.,López,S.,2004.Characterization of rotavirus cell entry.J.Virol.78(March(5)),2310–2318.
Santos,N.,Hoshino,Y.,2005.Global distribution of rotavirus serotypes/genotypes and its implication for the development and implementation of an effective rotavirus vaccine.Rev.Med.Virol.15(January–February(1)),29–56. Santosham,M.,Moulton,L.H.,Reid,R.,Croll,J.,Weatherholt,R.,Ward,R.,Forro, J.,Zito,E.,Mack,M.,Brenneman,G.,Davidson,B.L.,1997.Ef?cacy and safety of high-dose rhesus-human reassortant rotavirus vaccine in Native American populations.J.Pediatr.131(October(4)),632–638.
Sapparapu,G.,Sims,A.L.,Aiyegbo,M.S.,Shaikh,F.Y.,Harth,E.M.,Crowe Jr.,J.E.,2013.
Intracellular neutralization of a virus using a cell-penetrating molecular trans-porter.Nanomedicine(Lond.)(November)(Epub ahead of print).
Sarker,S.A.,J?kel,M.,Sultana,S.,Alam,N.H.,Bardhan,P.K.,Chisti,M.J.,Salam,M.A., Theis,W.,Hammarstr?m,L.,Frenken,L.G.,2013.Anti-rotavirus protein reduces stool output in infants with diarrhea:a randomized placebo-controlled trial.
Gastroenterology145(October(4)),740–748.e8.
Saulsbury,F.T.,Winkelstein,J.A.,Yolken,R.H.,1980.Chronic rotavirus infection in immunode?ciency.J.Pediatr.97(July(1)),61–65.
Schwartz-Cornil,I.,Benureau,Y.,Greenberg,H.,Hendrickson,B.A.,Cohen,J.,2002.
Heterologous protection induced by the inner capsid proteins of rotavirus requires transcytosis of mucosal immunoglobulins.J.Virol.76(August(16)), 8110–8117.
【高中】2017人教版高中物理必修一第一章运动的描述单元检测
【关键字】高中 【成才之路】2015-2016学年高中物理第一章运动的描述限时检测 新人教版必修1 本卷分第Ⅰ卷(选择题)和第Ⅱ卷(非选择题)两部分。满分100分，时间90分钟。 第Ⅰ卷(选择题共40分) 一、选择题(共10小题，每小题4分，共40分，在每小题给出的四个选项中，第1～6小题只有一个选项符合题目要求，第7～10小题有多个选项符合题目要求，全部选对的得4分，选不全的得2分，有选错或不答的得0分) 1.如图所示是体育摄影中“追拍法”的成功之作，摄影师眼中清晰的运动员是运动的，而模糊的背景是运动的，摄影师用自己的方式表达了运动的美。请问摄影师选择的参考系是( ) A．大地B．太阳 C．自身D．步行的人 答案：C 解析：日常生活中的许多运动现象实际上都是站在某一参考系的角度去描述的，本题中运动员是运动的，选择的是相对运动员运动的物体，故选项C是正确的。 2．如图所示，下列物体或人可以看成质点的是( ) A．研究从北京开往天津的一列高速列车的速率 B．研究绕月球运动的“嫦娥二号”卫星的运行姿态 C．体操运动员在单杠比赛中 D．表演精彩芭蕾舞的演员 答案：A 解析：研究卫星的飞行姿态时，不能把卫星视为质点，B错；完成单杠动作的运动员和表演芭蕾舞的演员，他们的姿态、肢体动作是需要研究的，不能把他们看成质点，C、D错；从北京开往天津的高速列车的形状、大小对于所研究的问题可忽略，可看成质点，A正确。 3．(长春市第十一中学2014～2015学年高一上学期检测)下列说法中正确的是( ) A．平均速率等于平均速度的大小 B．长春市十一高中7：20学生开始上课，其中“7：指的是时间 C．仁川亚运会的赛跑中，运动员跑完全程的位移和路程的大小相等 D．速率为瞬时速度的大小，速率是标量 答案：D 解析：平均速度是物体的位移与时间的比值，是矢量，所以A错误；“7：20”指的是时
高一物理第一章《运动的描述》单元测试试题A卷
高一物理单元测试试题 第一章运动的描述 时间40分钟，赋分100分 一、本题共10小题，每小题4分，共40分.在每小题给出的四个选项中，有的小题只有一个选项正 确，有的小题有多个选项正确.全部选对的得4分，选不全的得2分，有选错或不答的得0分. 1．某校高一的新同学分别乘两辆汽车去市公园游玩。两辆汽车在平直公路上运动，甲车内一同学看见乙车没有运动，而乙车内一同学看见路旁的树木向西移动。如果以地面为参考系，那么，上述观察说明 A．甲车不动，乙车向东运动B．乙车不动，甲车向东运动 C．甲车向西运动，乙车向东运动D．甲、乙两车以相同的速度都向东运动 2．下列关于质点的说法中，正确的是 A．质点是一个理想化模型，实际上并不存在，所以，引入这个概念没有多大意义 B．只有体积很小的物体才能看作质点 C．凡轻小的物体，皆可看作质点 D．如果物体的形状和大小对所研究的问题属于无关或次要因素时，即可把物体看作质点 3．某人沿着半径为R的水平圆周跑道跑了1.75圈时，他的 A．路程和位移的大小均为3.5πR B．路程和位移的大小均为2R C．路程为3.5πR、位移的大小为2R D．路程为0.5πR、位移的大小为2R 4．甲、乙两小分队进行军事演习，指挥部通过现代通信设备，在屏幕上观察到两小分队的具体行军路线如图所示，两小分队同时同地由O点出发，最后同时到达A点，下列说法中正确的是 A．小分队行军路程s甲＞s乙 B．小分队平均速度v甲＞v乙 C．y-x图象表示的是速率v-t图象 D．y-x图象表示的是位移s-t图象 5．某中学正在举行班级对抗赛，张明明同学是短跑运动员，在百米竞赛中，测得他在5 s末的速度为10.4 m/s，10 s末到达终点的速度为10.2 m/s，则他在全程中的平均速度为 A．10.4 m/s B．10.3 m/s C．10.2 m/s D．10m/s 6．下面的几个速度中表示平均速度的是 A．子弹射出枪口的速度是800 m/s，以790 m/s的速度击中目标
第一章.运动的描述
第一章.运动的描述 考点一：时刻与时间间隔的关系 时间间隔能展示运动的一个过程，时刻只能显示运动的一个瞬间。对一些关于时间间隔和时刻的表述，能够正确理解。如：第4s末、4s时、第5s初均为时刻；4s内、第4s、第2s至第4s内均为时间间隔。 区别：时刻在时间轴上表示一点，时间间隔在时间轴上表示一段。 考点二：路程与位移的关系 位移表示位置变化，用由初位置到末位置的有向线段表示，是矢量。路程是运动轨迹的长度，是标量。只有当物体做单向直线运动时，位移的大小.等于路程。一般情况下，路程邈移的大小。 考点三：速度与速率的关系 考点四：速度、加速度与速度变化量的关系 考点五：运动图象的理解及应用 由于图象能直观地表示出物理过程和各物理量之间的关系，所以在解题的过程中被广泛应用。在运动学中，经常用到的有x—t图象和v —t图象。 1.理解图象的含义 (1)x —t图象是描述位移随时间的变化规律 (2)v—t图象是描述速度随时间的变化规律 2.明确图象斜率的含义
(1)x—t图象中，图线的斜率表示速度 (2)v—t图象中，图线的斜率表示加速度 第二章?匀变速直线运动的研究 考点一：匀变速直线运动的基本公式和推理 1.基本公式 ⑴速度一时间关系式：v二V o at 1 2 ⑵ 位移一时间关系式：x =v0t at2 2 2 2 ⑶ 位移一速度关系式：V -V o =2ax 三个公式中的物理量只要知道任意三个，就可求出其余两个。 利用公式解题时注意：x、v、a为矢量及正、负号所代表的是方向的不同, 解题时要有正方向的规定。 2.常用推论 1 j (1) 平均速度公式：v v0v 2 (2) 一段时间中间时刻的瞬时速度等于这段时间内的平均速度: 2 2 v o v (3) 一段位移的中间位置的瞬时速度: (4) 任意两个连续相等的时间间隔( T)内位移之差为常数(逐差相等) ：x = X m - X n 二m - n aT2考点二：对运动图象的理解及应用 1.研究运动图象 (1)从图象识别物体的运动性质 (2)能认识图象的截距(即图象与纵轴或横轴的交点坐标)的意义 (3)能认识图象的斜率(即图象与横轴夹角的正切值)的意义 (4)能认识图象与坐标轴所围面积的物理意义 (5)能说明图象上任一点的物理意义 2. x —t图象和v—t图象的比较 如图所示是形状一样的图线在x —t图象和V—t图象中,
第一章运动的描述单元测试题及答案
第一章《运动的描述》单元测试题及答案． 运动的描述单元测试题 一、单项选择题。是质点的中，不能看作下1.列物体
）（ 计算从北京开往广州的的火车途中所用的时、A 间研究绕地球飞行的航天飞机相对地球的飞行、B 周期时，、沿地面翻滚前进的体操运动员C 比较两辆行驶中的车的快慢D、是正，确的中描系参关下2.列于考的述）（ A、参考系必须是和地面连在一起的物体、被研究的物体必须沿与参考系的连线运动B 参考系必须是正在做匀速直线运动的物体
或、C 是相对于地面静止的物体、参考系 是为了研究物体的运动而假定D A为不动的 那个物体B的半圆弧3.如右图，某一物体 沿两个半径为R C ，则它的位移和路程分别 C运动到由A 是 2 ( ) A、0，0 B、4 R向下， πR C、4πR向下、4R D、4R向下，2 πR
4.氢气球升到离地面80m的高空时从上面掉落下一物体，物体又上升了10m后开始下落，若取 向上为正，则物体从掉落开始至最终落在地面时的位移和经过的路程分别为 （） A、80m，100m B、－80m，100m C、80m，100 m D、－90 m，180 m 5.下列关于平均速度和瞬时速度的说法中
正确的是 （） A、做变速运动的物体在相同时间间隔里的平均速度是相同的 B、瞬时速度就是运动的物体在一段较短的时间内的平均速度 C、平均速度就是初末时刻瞬时速度的平均值 D、某物体在某段时间里的瞬时速度都为零，则该物体在这段时间内静止 是的确正，法说的度速加于关列下 6.( ) A、物体的速度越大，加速度也就越大 B、物体的速度为零，加速度也一定为零 3 C、物体的加速度大小等于速度的变化量与时间的比值 D、物体的加速度的方向和速度的方向总是一致
第一章运动的描述
第一篇力学基础 第一章运动的描述 教学时间：5学时 本章教学目标：理解运动的绝对性和相对性；理解位置矢量和位移的不同含义；能够根据运动方程求速度和加速度，能够根据速度和加速度求运动方程的表达式；掌握伽利略变换公式，能够根据相对运动公式解决相关问题。 教学方式：讲授法、讨论法等 教学重点：能够根据运动方程求速度和加速度，能够根据速度和加速度求运动方程的表达式。 在经典力学中，通常将力学分为运动学、动力学和静力学。本章只研究运动学规律。运动学是从几何的观点来描述物体的运动，即研究物体的空间位置随时间的变化关系，不涉及引发物体运动和改变运动状态的原因。 §1.1 参考系坐标系物理模型 一、运动的绝对性和相对性 运动是物质的固有属性。从这种意义上讲，运动是绝对的。 但我们所讨论的运动，还不是这种哲学意义上的广义运动。 即使以机械运动形式而言，任何物体在任何时刻都在不停地运动着。例如，地球就在自转的同时绕太阳公转，太阳又相对于银河系中心以大约250 km/s。的速率运动，而我们所处的银河系又相对于其他银河系大约以600 km/s。的速率运动着。总之，绝对不运动的物体是不存在的。 然而运动又是相对的。
因为我们所研究的物体的运动，都是在一定的环境和特定的条件下运动。例如，当我们说一列火车开动了，这显然是指火车相对于地球(即车站)而言的因此离开特定的环境、特定的条件谈论运动没有任何意义正如恩格斯所说：“单个物体的运动是不存在的——只有在相对的意义下才可以谈运动。” 二、参考系 运动是绝对的，但运动的描述却是相对的因此，在确定研究对象的位置时，必须先选定一个标准物体(或相对静止的几个物体)作为基准；那么这个被选作标准的物体或物体群，就称为参考系。 同一物体的运动，由于我们所选参考系不同，对其运动的描述就会不同。 从运动学的角度讲，参考系的选择是任意的，通常以对问题的研究最方便最简单为原则。研究地球上物体的运动，在大多数情况下，以地球为参考系最为方便(以后如不作特别说明，研究地面上物体的运动，都是以地球为参考系)但是。当我们在地球上发射人造“宇宙小天体”时，则应以太阳为参考系。 三、坐标系 要想定量地描述物体的运动，就必须在参考系上建立适当的坐标系。 在力学中常用的有直角坐标系。根据需要，我们也可选用极坐标系、自然坐标系、球面坐标系或柱面坐标系等。 总的说来，当参考系选定后，无论选择何种坐标系，物体的运动性质都不会改变。然而，坐标系选择得当，可使计算简化。 四、物理模型 任何一个真实的物理过程都是极其复杂的。为了寻找过程中最本质、最基本的规律，我们总是根据所提问题(或所要回答的问题)，对真实过程进行理想化的简化，然后经过抽象提出一个可供数学描述的物理模型 现在我们所提的问题是确定物体在空间的位置。若物体的线度比它运动的空间范围小很多时，例如绕太阳公转的地球和调度室中铁路运行图上的列车等；或当物
第一章 运动的描述单元测试(含答案)
《运动的描述》单元测试 一．选择题（每题4分，共36分有的小题只有一个答案正确，有的小题有多个答案正确）1．“小小竹排江中游，巍巍青山两岸走。”这两句诗描述的运动的参考系分别是（） A．竹排，流水 B．流水，青山 C．青山，河岸 D．河岸，竹排 2．以下几种关于质点的说法，你认为正确的是（） A．只有体积很小或质量很小的物体才可发看作质点 B．只要物体运动得不是很快，物体就可以看作质点 C．质点是一种特殊的实际物体D．物体的大小和形状在所研究的问题中起的作用很小，可以忽略不计时，我们就可以把物体看作质点 3．下列说法正确的是（） A．“北京时间10点整”，指的是时间，一节课是40min，指的是时刻 B．列车在上海站停了20min，指的是时间 C．在有些情况下，时间就是时刻，时刻就是时间 D．电台报时时说：“现在是北京时间8点整”，这里实际上指的是时刻 4．短跑运动员在100m竞赛中，测得75m速度为9m/s，10s末到达终点时速度为10.2m/s，则运动员在全程中的平均速度为（） A ． 9 m/s B ． 9.6 m/s C ． 10 m/s D． 10.2 m/s 5．下列说法中，正确的是（） A．质点做直线运动时，其位移的大小和路程一定相等 B．质点做曲线运动时，某段时间内位移的大小一定小于路程 C．两个位移相同的质点，它们所通过的路程一定相等 D ．两个质点通过相同的路程，它们的位移大小一定相等 6．氢氢气球升到离地面80m的高空时从上面掉落下一物体，物体又上升了10m后开始下落，若取向上为正，则物体从掉落开始至地面时位移和经过的路程分别为（） A．80m，100m B．-80m，100m C．80m，100 m D．-90 m，180 m 7．如图所示为同一打点计时器在四条水平运动的纸带上打出的点,其中a , b间的平均速度最大的是哪一条? 8.以下关于加速度的说法中，正确的是： A．加速度为0的物体一定处于静止状态 B．物体的加速度减小，其速度必随之减小C．物体的加速度增加，其速度不一定增大 D．物体的加速度越大，其速度变化越快9. 关于速度，速度改变量，加速度，正确的说法是： A．物体运动的速度改变量很大，它的加速度一定很大 B．速度很大的物体，其加速度可以很小，可以为零 C．某时刻物体的速度为零，其加速度不可能为零 D．加速度很大时，运动物体的速度一定很大
第一章运动的描述
第一章运动的描述 【本章阅读材料】 一．参考系 1.定义：在描述一个物体的运动时，选来作为标准的假定不动的物体，叫做参考系。 2.对同一运动，取不同的参考系，观察的结果可能不同。 3.运动学中的同一公式中涉及的各物理量应以同一参考系为标准，如果没有特别指明，都是取地面为参考系。 二．质点 1.定义：质点是指有质量而不考虑大小和形状的物体。 2.质点是物理学中一个理想化模型，能否将物体看作质点，取决于所研究的具体问题，而不是取决于这一物体的大小、形状及质量，只有当所研究物体的大小和形状对所研究的问题没有影响或影响很小，可以将其形状和大小忽略时，才能将物体看作质点。 三．时间与时刻 1.时刻：指某一瞬时，在时间轴上表示为某一点。 2.时间：指两个时刻之间的间隔，在时间轴上表示为两点间线段的长度。 3.时刻与物体运动过程中的某一位置相对应，时间与物体运动过程中的位移（或路程）相对应。 四．位移和路程 1.位移：表示物体位置的变化，是一个矢量，物体的位移是指从初位置到末位置的有向线段，其大小就是此线段的长度，方向从初位置指向末位置。 2.路程：路程等于运动轨迹的长度，是一个标量。 当物体做单向直线运动时，位移的大小等于路程。 五．速度、平均速度、瞬时速度 1.速度：是表示质点运动快慢的物理量，在匀速直线运动中它等于位移与发生这段位移所用时间的比值，速度是矢量，它的方向就是物体运动的方向。
2.平均速度：物体所发生的位移跟发生这一位移所用时间的比值叫这段时间内的平均速度，即t v x =，平均速度是矢量，其方向就是相应位移的方向。仅能粗略描述物体的运动的快慢程度。 3.瞬时速度：运动物体经过某一时刻（或某一位置）的速度，其方向就是物体经过某有一位置时的运动方向。大小称之为速率。 它能精确描述物体运动的快慢程度。 （4）极短时间内的平均速度等于某时刻的瞬时速度。 六．加速度 1.加速度是描述物体速度变化快慢的的物理量，是一个矢量，方向与速度变化的方向相同。 2.做匀变速直线运动的物体，速度的变化量与发生这一变化所需时间的比值叫加速度，即t v v t v a 0-=??= 3.对加速度的理解要点： （1）加速度的大小和速度无直接关系。质点的运动的速度大，加速度 不一定大；速度小，其加速度不一定小；速度为零，其加速度不一定为零； （2）加速度的方向不一定和速度方向相同。质点做加速直线运动时，加速度与速度方向相同；质点做减速直线运动时，加速度与速度方向相反； （3）物体做加速直线运动还是做减速直线运动，判断的依据是加速度的方向和速度方向是相同还是相反，只要加速度方向跟速度方向相同，物体的速度一定增大（即加速直线运动），只要加速度方向跟速度方向相反，物体的速度一定减小（即减速直线运动）。
第1章运动的描述章末检测
第一章运动的描述 (时间：90分钟满分：100分) 一、选择题(本题共10小题，每小题4分，共40分) 1．2008年9月25日晚21点10分，在九泉卫星发射中心将我国自行研制的“神舟”七号载人航天飞船成功地送上太空，飞船绕地球飞行一圈时间为90分钟，则() A．“21点10分”和“90分钟”前者表示“时刻”后者表示“时间” B．飞船绕地球飞行一圈，它的位移和路程都为0 C．飞船绕地球飞行一圈平均速度为0，但它在每一时刻的瞬时速度都不为0 D．地面卫星控制中心在对飞船进行飞行姿态调整时可以将飞船看成质点 2．明代诗人曾写下这样一首诗：“空手把锄头，步行骑水牛；人在桥上走，桥流水不流．”其“桥流水不流”中的“桥流”应理解成其选择的参考系是() A．水B．桥C．人D．地面 3．物体沿一直线运动，下列说法中正确的是() A．物体在第一秒末的速度是5 m/s，则物体在第一秒内的位移一定是5 m B．物体在第一秒内的平均速度是5 m/s，则物体在第一秒内的位移一定是5 m C．物体在某段时间内的平均速度是5 m/s，则物体在每一秒内的位移都是5 m D．物体在某段位移内的平均速度是5 m/s，则物体在经过这段位移一半时的速度一定是5 m/s 4．甲、乙两个物体在同一直线上运动(始终没有相遇)，当规定向东为正方向时，它们的加速度分别为a甲＝4 m/s2，a乙＝－4 m/s2.下列对甲、乙两物体运动情况的判断中，正确的是() A．甲的加速度大于乙的加速度 B．甲、乙两物体的运动方向一定相反 C．甲的加速度方向和速度方向一致，乙的加速度方向和速度方向相反 D．甲、乙两物体的速度都有可能越来越大 5．一辆汽车从静止开始由甲地出发，沿平直公路开往乙地，汽车先做匀加速运动．接着做匀减速运动，到达乙地刚好停止，其速度图象如图1所示，那么在0～t0和t0～3t0两段时间内() 图1 A．加速度大小之比为2∶1，且方向相反 B．位移大小之比为1∶2，且方向相反 C．平均速度大小之比为2∶1 D．平均速度大小之比为1∶1 6．物体由静止开始运动，加速度恒定，在第7 s内的初速度是2.6 m/s，则物体的加速度是() A．0.46 m/s2B．0.37 m/s2 C．2.6 m/s2D．0.43 m/s2 7. 图2
第一章运动的描述
第1章 怎样描述物体的运动测评 (时间：45分钟，满分：100分) 一、本题共8小题，每小题5分，共40分不定项选择． 1．如图所示的是体育摄影中“追拍法”的成功之作，摄影师眼中清晰的运动员是静止的，而模糊的背景是运动的，摄影师用自己的方式表达了运动的美．请问摄影师选择的参考系是 A ．大地 B ．太阳 C ．运动员 D ．步行的人 2．在下列各种情况中，物体可看做质点的是 A ．正在做课间操的同学们都可以看做质点 B ．从地面控制中心的屏幕上观察“嫦娥一号”的运动情况 时，“嫦娥一号”可以看做质点 C ．观察航空母舰上的舰载飞机起飞时，可以把航空母舰看做质点 D ．在作战地图上确定航空母舰的准确位置时，可以把航空母舰看做质点 3．中国飞人刘翔，在2008年5月10日的大阪国际田径大奖赛男子110米栏的比赛中，以13秒19的成绩如愿摘金，在大阪大奖赛上夺得五连冠．关于比赛的下列说法中正确的是 A ．110 m 是刘翔比赛中位移的大小 B ．13秒19是刘翔夺冠的时刻 C ．刘翔比赛中的平均速度约是8.3 m/s D ．刘翔经过终点线时的速度一定等于8.3 m/s 4．让一个小球从2 m 高处落下，被地面弹回，在1 m 高处被接住，则小球在这一过程中 A ．位移大小是3 m B ．位移大小是1 m C ．位移大小是2 m D ．路程是2 m 5．(2008山东学业水平测试，4)下列事例中有关速度的说法，正确的是 A ．汽车速度计上显示80 km/h ，指的是平均速度 B ．某高速公路上的限速为110 km/h, 指的是平均速度 C ．火车从济南到北京的速度约为220 km/h, 指的是瞬时速度 D ．子弹以900 km/h 的速度从枪口射出，指的是瞬时速度 6．下列对加速度的定义式a ＝Δv Δt 的理解正确的是 A ．加速度a 与速度变化量Δv 成正比 B ．加速度a 的大小由速度变化量Δv 决定 C ．加速度a 的方向与Δv 方向相同 D ．加速度a 决定于速度变化率Δv Δt 7．如图所示分别为甲、乙两物体的st 图像，则下列关于甲、乙两物体的速度都正确的是 A ．v 甲＝30 m/s v 乙＝30 m/s B ．v 甲＝20 m/s v 乙＝30 m/s C ．v 甲＝30 m/s v 乙＝20 m/s D ．v 甲＝45 m/s v 乙＝15 m/s 8．甲、乙两个物体在同一直线上运动的vt 图像如图所示，由 图像可知两物体 A ．速度方向相同，加速度方向相反 B ．速度方向相反，加速度方 向相同 C ．甲的加速度大于乙的加速度 D ．甲的加速度小于乙的加速度 第Ⅱ卷(非选择题 共60分) 二、实验题：本题15分，把答案填在题中横线上． 9．在研究匀变速直线运动的实验中，一记录小车运动情况的纸带 如图所示，图中A 、B 、C 、D 、E 、F 为相邻的计数点，相邻的计数点 间的时间间隔为T ＝0.1 s ．求： (1)各点的瞬时速度v B ＝______m/s ，v C ＝______m/s ，v D ＝______m/s ，v E ＝______m/s. (2)打点计时器打A 点开始计时，在下面图中作出小车的vt 图像．
人教版物理必修一试题第一章：运动的描述单元练习题(新课标有答案).docx
& 鑫达捷致力于精品文档精心制作仅供参考& 高中物理学习材料 高一物理(必修1)第一章<<运动的描述>>单元练习 班级姓名：座号 一、选择题（不定项） 1.下面关于质点的说法正确的是：（ C ） A、地球很大，不能看作质点 B、原子核很小，可以看作质点 C、研究地球公转时可把地球看作质点 D、研究地球自转时可把地球看作质点 2.一小球从4m高处落下，被地面弹回，在1m高处被接住，则小球的路程和位移大小分别为： （ A ） A、5m，3m B、4m，1m C、4m，3m D、 5m，5m 3.某人坐在甲船看到乙船在运动，那么相对河岸两船的运动情况不可能的是（ D ） A、甲船不动，乙船在运动 B、甲船运动，乙船不动 C、甲、乙两船都在运动 D、甲、乙两船都以相同的速度运动 4.两辆汽车在平直公路上行驶，甲车内的人看见树木向东移动，乙车内的人发现甲车没有运动，如果以 大地为参考系，上述事实说明：（ D ） A、甲车向西运动，乙车不动 B、乙车向西运动，甲车不动 C、甲车向西运动，乙车向东运动 D、甲、乙两车以相同速度向西运动 5.下列说法正确的是：（ B ） A、质点一定是体积很小、质量很小的物体 B、地球虽大，且有自转，但有时仍可将地球看作质点 C、研究自行车的运动时，因为车轮在转动，所以无论什么情况下，自行车都不能看成质点 D、当研究一列火车全部通过桥所需的时间，因为火车上各点的运动状态相同，所以可以把火车视为 质点 6.关于位移和路程的说法中正确的是：（ CD ） A、位移的大小和路程的大小总是相等的，只不过位移是矢量，而路程是标量 B、位移是描述直线运动的，路程是描述曲线运动的 C、位移取决于始末位置，路程取决于实际运动的路线 D、运动物体的路程总大于或等于位移的大小 7.如图所示，一质点绕半径为R的圆周运动，当质点由A点运动到B点时，其位移大小和路程分别是（ C ） A．R R
1-：第一章 运动的描述(知识框架)
第一章 运动的描述（知识框架） - 1 - 第一章 运动的描述（知识框架） 运 动 的 描 述 质点：形状、大小可忽略不计的有质量的点 物体可看成质点的条件：物体的大小、形状对研究问题的影响可忽略不计 参考系：描述一个物体运动时，用来选作标准的另外的物体 坐标系：用来准确描述物体位置及位置变化 基本概念 概念对比 时刻：是指某一瞬时，在时间轴上是一个点 时间：是时间间隔的简称，指一段持续的时间间隔， 两个时刻的间隔表示时间 路程：质点实际运动的轨迹的长度；单位m 。 位移：从物体运动的起点指向运动的终点的有向线段，表示位置的变化； 单位：m 矢量：既有大小，又有方向的物理量；如：速度、位移 标量：只有大小，没有方向的物理量；如：路程、时间 定义：物体运动的位移与时间的比值 物理意义：表示物体运动的快慢 速度 公式：t x t x =??=ν；单位：m/s 矢量性：矢量 定义：某一过程中的一段位移与其所对应的时间的比值 物理意义：粗略地表示物体运动的快慢 公式：t x t x =? ?= ν ；单位：m/s 矢量性：矢量 平均速度 速率：表示速度的大小；标量。 平均速率：表示某义过程中的一段路程与其所用的时间的比值 是一个标量 速率 速度 定义：速度的变化量与时间的比值 物理意义：表示速度变化的快慢 公式： t v v t v a t 0-=??=; 单位：m/s 2 矢量性：矢量，与速度变化量方向相同 加速度 实验 打点计时器分类：电磁打点计时器和电火花打点计时器 振动频率：均为50Hz ，即每隔0.02s 打一个点 纸带分析：a.可计算物体运动的平均速度 b ．粗略计算瞬时速度
人教版高一物理上册 运动的描述检测题(Word版 含答案)
一、第一章运动的描述易错题培优（难） 1．质点做直线运动的v-t 图象如图所示，则（） A．3 ~ 4 s 内质点做匀减速直线运动 B．3 s 末质点的速度为零，且运动方向改变 C．0 ~ 2 s 内质点做匀加速直线运动，4 ~ 6 s 内质点做匀减速直线运动，加速度大小均为 2 m/s2 D．6 s内质点发生的位移为 8 m 【答案】BC 【解析】 试题分析：矢量的负号，只表示物体运动的方向，不参与大小的比较，所以3 s～4 s内质点的速度负方向增大，所以做加速运动，A错误，3s质点的速度为零，之后开始向负方向运动，运动方向发生变化，B错误，图线的斜率表示物体运动的加速度，所以0～2 s内质点做匀加速直线运动，4 s～6 s内质点做匀减速直线运动，加速度大小均为2 m/s2，C正确，v-t图像围成的面积表示物体的位移，所以6 s内质点发生的位移为0，D错误， 考点：考查了对v-t图像的理解 点评：做本题的关键是理解v-t图像的斜率表示运动的加速度，围成的面积表示运动的位移，负面积表示负方向位移， 2．如图，直线a和曲线b分别是在平直公路上行驶的汽车a和b的位置一时间（x一t）图线，由图可知 A．在时刻t1，a车追上b车 B．在时刻t2，a、b两车运动方向相反 C．在t1到t2这段时间内，b车的速率先减少后增加 D．在t1到t2这段时间内，b车的速率一直比a车大 【答案】BC 【解析】 【分析】
【详解】 由x—t图象可知，在0-t1时间内，b追a，t1时刻相遇，所以A错误；在时刻t2，b的斜率为负，则b的速度与x方向相反，所以B正确；b图象在最高点的斜率为零，所以速度为零，故b的速度先减小为零，再反向增大，所以C正确，D错误． 3．高速公路上用位移传感器测车速，它的原理如图所示，汽车D向右匀速运动，仪器C 在某一时刻发射超声波脉冲（即持续时间很短的一束超声波），经过时间t1接收到被D反射回来的超声波，过一小段时间后又发射一个超声波脉冲，发出后经过时间t2再次接收到反射回来的信号，已知超声波传播的速度为v0，两次发射超声波脉冲的时间间隔为△t，则下面说法正确的是（） A．第一次脉冲测得汽车和仪器C的距离为 01 1 2 v t B．第二次脉冲测得汽车和仪器C的距离为02 v t C．位移传感器在两次测量期间，汽车前进距离为 021 1 () 2 v t t- D．测得汽车前进速度为021 21 () 2 v t t t t t - +?- 【答案】ACD 【解析】 【分析】 【详解】 AB．超声波是匀速运动的，往返时间相同，第一次脉冲测得汽车和仪器C的距离为01 1 2 v t，第二次脉冲测得汽车和仪器C的距离为 02 1 2 v t，故A正确，B错误； C．则两次测量期间，汽车前进的距离为 () 021 1 2 s v t t =- 故C正确； D．超声波两次追上汽车的时间间隔为 12 22 t t t t ' ?=?-+ 故速度
少数民族传统节日表汇编
中国少数民族主要节日 民族主要节日时间 阿昌族火把节农历六月二十五日会街节农历九月初十 泼水节农历二月二十九日撒神农历七月初一 尝新节农历八月十五日 白族三月街农历三月十五日火把节农历六月二十四日渔潭会农历八月十五日 保安族圣纪节伊斯兰教历三月十二日开斋节伊斯兰教历九月三十日古尔邦节伊斯兰教历十二月十日 布郎族开门节傣历十二月十五日关门节傣历九月十五日泼火节农历二月十九日 布依族 六月六农历六月初六 三月三农历三月初三朝鲜族 元日农历正月初一 上元节农历正月初五 寒食节农历四月初五 端午农历五月初五 哈尼族 十月节农历十月初一 六月节农历六月二十四日 哈萨克族 圣纪节伊斯兰教历三月十二日 开斋节伊斯兰教历九月三十日 古尔邦节伊斯兰教历十二月十日赫哲族赫哲年农历正月初一 回族 圣纪节伊斯兰教历三月十二日 开斋节伊斯兰教历九月三十日 古尔邦节伊斯兰教历十二月十日基诺族 打铁节农历一月 火把节农历六月 京族哈节农历六月初十 德昂族泼水节农历四月十五日 东乡族 圣纪节伊斯兰教历三月十二日 开斋节伊斯兰教历九月三十日 古尔邦节伊斯兰教历十二月十日
四月八农历四月初八 朝鲜族元日农历正月初一上元节农历正月初五寒食节农历四月初五端午农历五月初五 哈尼族 十月节农历十月初一 六月节农历六月二十四日 哈萨克族圣纪节伊斯兰教历三月十二日开斋节伊斯兰教历九月三十日古尔邦节伊斯兰教历十二月十日 赫哲族赫哲年农历正月初一 回族圣纪节伊斯兰教历三月十二日开斋节伊斯兰教历九月三十日古尔邦节伊斯兰教历十二月十日 基诺族 打铁节农历一月 火把节农历六月 京族哈节农历六月初十 德昂族泼水节农历四月十五日 东乡族圣纪节伊斯兰教历三月十二日
第一章 运动的描述
§1.1 质点、参考系和坐标系 一.机械运动：一个物体相对于另一个物体的位置变化，叫做机械运动（简称运动）。机械运动包括：平动、转动、机械振动。物体的运动轨迹可能是直线也可能是曲 线。 二.质点：一个有质量的点，把实际物体看做一个有质量的点。质点是一个理想化的物 理模型，实际并不存在，是为了方便描述物体的运动将实际物体抽象成一个点。这个点不同于几何点，尽管它们都是零维（零维指没有长、宽、高的维）的，但质点是有质量的，它代表着实际的物体。把一个实际的物体看做质点是抓住了事物的主要矛盾而忽略了次要因素，这也是物理学研究的一种很重要的方法。今后在物理学中经常会用到这种方法。 三.实际物体能被看做质点的条件：实际物体能否被看做质点要看问题本身，同一 个物体在甲问题中能看做质点而在乙问题中就不能看成质点了。具体要注意以下几点：①如果物体的几何形状和尺度对研究问题本身影响很小，以至于可以不考虑物体的形状时可以把物体看做质点。 比如，我们要计算一列火车从北京到上海的时间，因为火车的几何尺度与北京到上海的距离无法比拟，因此我们可以把火车看成质点。 ②作平动的物体一般可以被视为质点，但这也不是绝对的。 比如，火车的运动可以被看做平动，我们要计算一列火车从北京到上海的时间，因为火车的几何尺度与北京到上海的距离无法比拟，因此我们可以把火车看成质点。但是要计算一列火车穿越一个山洞的时间时，就不能把火车看做质点了。 ③作转动的物体一般不能看作质点，但这也不是绝对的。 比如，研究一根绕固定轴转动的木棒的运动情况，就不能把木棒看作质点。但是研究作圆周运动的物体时可以把物体看做质点。 ④并不是很小的物体就一定能视为质点，而很大的物体就不能视为质点。 在高中阶段我们所接触到的物体大部分是可以被视为质点的。 例题： 1.关于运动员和球类能否看成质点，以下说法正确的是（） A.研究跳高运动员的起跳和过杆动作时，可以把运动员看成质点 B.研究花样滑冰运动员的冰上动作时，能把运动员看成质点 C.研究足球的射门速度时，可以把足球看成质点 D.研究乒乓球弧圈球的接球时，能把乒乓球看成质点 2.在下列物体的运动中，可把物体视为质点的是（） A.研究“神州七号”绕地球运动的圈数时 B.对“神州七号”进行姿态调整时 C.研究跳水运动员在空中的翻滚运动时 D.研究从滑梯上滑下的小孩 四.参考系：为了描述物体的运动，需要先选定一个假定不动的物体作标准，看要描述 的那个物体相对于这个标准物体是如何运动的，这个被选作标准的物体就叫做参考系（参照物）。
人教版必修一第一章《运动的描述》单元教学设计1(精品).doc
第一章运动的描述 （一）全章知识脉络，知识体系 基本概念图解
一、质点、参考系、位移、路程 1.下列物体中，不能看作质点的是（） A.计算从北京开往上海的途中，与上海的距离时的火车 B.研究航天飞机相对地球的飞行周期时，绕地球飞行的航天飞机 C.沿地面翻滚前进的体操运动员 D. 比较两辆行驶中的车的快慢 2.下列关于参考系的描述中，正确的是（） A.参考系必须是和地面连在一起的物体 B.被研究的物体必须沿与参考系的连线运动 C.参考系必须是正在做匀速直线运动的物体或是相对于地面静止的物体 D.参考系是为了研究物体的运动而假定为不动的那个物体 四、计算题(共27分) 16.（8分）已知一汽车在平直公路上运动，它的位移一时间图象如图（甲）所示. （1）根据图象在图（乙）所示的位置坐标轴上标出A、B、C、D、E各点代表的汽车的位置 （2）求出下列各段时间内汽车的路程和位移大小 ①第 l h内．②前6 h内③前7 h内④前8 h内 17. （9分）A、B、C三地彼此间的距离均为 a，如图所示物体以每秒走完距离a的速度从A点出发，沿折线经B、C点又回到A点试分析说明从运动开始经1 s、2 s、
3 s ，物体的位移大小和路程各为多少？ 18.（10分）如图所示为一物体沿直线运动的s-t 图象，根据图象：求 （1）第2 s 内的位移，第4 s 内的位移，前5 s 的总路程和位移 （2）各段的速度 （3）画出对应的v -t 图象 二、速度（瞬时速度、平均速度） 1．试判断下面的几个速度中哪个是瞬时速度 A ．子弹出枪口的速度是800 m/s ，以790 m/s 的速度击中目标 B ．汽车从甲站行驶到乙站的速度是40 km/h C ．汽车通过站牌时的速度是72 km/h D ．小球第3ｓ末的速度是6 m/s 2．下列说法中正确的是 A ．做匀速直线运动的物体，相等时间内的位移相等 B ．做匀速直线运动的物体，任一时刻的瞬时速度都相等 C ．任意时间内的平均速度都相等的运动是匀速直线运动 D ．如果物体运动的路程跟所需时间的比值是一个恒量，则此运动是匀速直线运动 3．下面关于瞬时速度和平均速度的说法正确的是 A ．若物体在某段时间内每时刻的瞬时速度都等于零，则它在这段时间内的平均速度一 定等于零 B ．若物体在某段时间内的平均速度等于零，则它在这段时间内任一时刻的瞬时速度一 定等于零 B
高一物理必修一第一章《运动的描述》单元测试题(含详细解答)[1]
《运动的描述》单元测试题 本卷分第Ⅰ卷(选择题)和第Ⅱ卷(非选择题)两部分．满分100分，时间90分钟． 第Ⅰ卷(选择题共40分) 一、选择题(共10小题，每小题4分，共40分，在每小题给出的四个选项中，有的小题只有一个选项符合题目要求，有些小题有多个选项符合题目要求，全部选对的得4分，选不全的得2分，有选错或不答的得0分) 1．下列关于质点的说法正确的是() A．研究和观察日食时，可以把太阳看成质点 B．研究地球的公转时，可以把地球看成质点 C．研究地球的自转时，可以把地球看成质点 D．原子核很小，必须把它看成质点 2．(广东惠阳08－09学年高一上学期期中)2008年9月25日晚21点10分，我国在九泉卫星发射中心将我国自行研制的“神舟7号”宇宙飞船成功地送上太空，飞船绕地球飞行一圈时间为90分钟．则() A．“21点10分”和“90分钟”前者表示“时刻”后者表示“时间” B．卫星绕地球飞行一圈，它的位移和路程都为0 C．卫星绕地球飞行一圈平均速度为0，但它在每一时刻的瞬时速度都不为0 D．地面卫星控制中心在对飞船进行飞行姿态调整时可以将飞船看作质点 3．甲物体以乙物体为参考系是静止的，甲物体以丙物体为参考系又是运动的，那么，以乙物体为参考系，丙物体的运动情况是() A．一定是静止的 B．运动或静止都有可能 C．一定是运动的 D．条件不足，无法判断 ． 4．(福建厦门一中09－10学年高一上学期期中)两个人以相同的速率同时从圆形轨道的A点出发，分别沿ABC和ADC行走，如图所示，当他们相遇时不相同的物理量是() A．速度B．位移 C．路程D．速率
5．两个质点甲和乙，同时由同一地点向同一方向做直线运动，它们的v －t 图象如图所示，则下列说法中正确的是( ) A ．质点乙静止，质点甲的初速度为零 B ．质点乙运动的速度大小、方向不变 C ．第2s 末质点甲、乙速度相同 D ．第2s 末质点甲、乙相遇 6．某人爬山，从山脚爬上山顶，然后又从原路返回到山脚，上山的平均速率为v 1，下山的平均速率为v 2，则往返的平均速度的大小和平均速率是( ) A.v 1＋v 22，v 1＋v 22 B.v 1－v 22，v 1－v 2 2 C ．0，v 1－v 2 v 1＋v 2 D ．0，2v 1v 2 v 1＋v 2 7．(银川一中09－10学年高一上学期期中)下列关于物体运动的说法，正确的是( ) A ．物体速度不为零，其加速度也一定不为零 B ．物体具有加速度时，它的速度可能不会改变 C ．物体的加速度变大时，速度也一定随之变大 D ．物体加速度方向改变时，速度方向可以保持不变 8．下表是四种交通工具的速度改变情况，下列说法正确的是( ) 初始速度(m/s) 经过时间(s) 末速度(m/s) ① 2 3 11 ② 0 3 6 ③ 0 20 6 ④ 100 20 A.①的速度变化最大，加速度最大 B ．②的速度变化最慢 C ．③的速度变化最快 D ．④的末速度最大，但加速度最小
第一章运动的描述
0（90分钟，满分100分） 00一、选择题（本大题有14小题，每小题2分，共28分） 0 1 ?使用刻度尺测长度时，下列说法不正确的是（） 0 A.放置刻度尺时，刻度尺应沿所测长度放置，并且必须从零刻度线量起 0 B.刻度尺读数时,视线要与尺面垂直，并要正对刻度线 0 C.读数时，要估读到分度值的下一位 0 D.记录时,要记下测量的数字和单位 0 2、用毫米刻度尺测量工件的长度，将其一端与10cm处的刻度线对准，另外一端0恰好与24 cm的刻度线对齐，次工件的长度记为（） 答 B .看台上坐着的观众 A . A 与 B B . A 与 C C . C 与 D D . B 与C 6 （2014?绵阳）汽车站并排停放着两辆大客车，甲车突然相对地面向后行驶，乙车仍相对地面静止，这时乙车上坐在座椅上的乘客却觉得乙车在向前行驶.则该乘客选择的参照物可能是（） A.乙车 B.甲车 C.房屋 D.树木 7、下列四个选项中，平均速度最大的是（ ） A.航模飞行器以60 m/min的速度匀速飞行100 m B.汽车以40km/h的速度在公路上匀速行驶200 m C.百米赛跑中运动员用12 s跑完全程 D.从30 m高处竖直下落的物体用了2 s 8、甲、乙两车分别从P、Q两点同时同向运动，它们的s--t图像分别如图a,b所示，经过6秒甲乙相遇。甲、乙的速度分别为V甲、V乙，P、Q间的距离为S 则（） 9、甲乙两物体从同一地点同时同方向做直线运动，其S---T图像如图所示，由图 像可知（） 第一章运动的描述C.地面 D .刘翔前方立着的栏 4、右图是甲、乙两辆同时从同一地点出发的小车的s-t图像，由图像可知（ 0 0 0 0 0 0 0 0 0 0 0 0 线 A. 7?20秒钟乙车做匀速直线运动 B .在0?5秒时间内，乙车的速度比甲车的速度大 C .第10秒钟时，甲、乙两车速度相同 D .经过5秒钟，甲车通过的路程比乙车大 5、如图所示的图象中，描述的是同一种运动形式的是（ ） S 4 V 4 5 4 v4 B D 两物体衣15 -20-内都嫩匀連逮功■且* ■ 第一章 运动的描述(人教版配套精练检测题)
第一章运动的描述 一、选择题 1．在研究下述运动时，能把物体看作质点的是( ) A．研究地球的自转 B．研究乒乓球的旋转 C．研究火车从北京运行到上海 D．研究悬挂的轻绳下系着的小钢球的摆动 2．关于参考系的选择，以下说法中正确的是( ) A．参考系必须选择静止不动的物体 B．任何物体都可以被选作参考系 C．参考系就是不动的物体 D．参考系必须是和地面连在一起的物体 3．下列说法中哪些表示的是时刻( ) A．2008年8月8日晚20∶00，第二十九届奥林匹克运动会在北京开幕 B．校运动会100 m赛跑的最好成绩是12.8 s C．学校早8∶00开始上课 D．人造地球卫星绕地球运行的最小周期是86 min 4．下列关于路程和位移的说法中，正确的是( ) A．位移为零时，路程一定为零 B．路程为零时，位移不一定为零 C．物体沿直线运动时，位移的大小可以等于路程 D．物体沿曲线运动时，位移的大小可以等于路程 5．一个质点在x轴上运动，各个时刻的位置坐标如下表，则此质点开始运动后在 前几秒内位移的大小最大的是( ) A．1 s B．2 s C．3 s D．4 s
6．图示为高速摄影机拍摄到的子弹穿过苹果瞬间的照片。该照片经过放大后分析出,在曝光时间内，子弹影像前后错开的距离约为子弹长度 的1%～2%。已知子弹飞行速度约为500 m/s，因此可 估算出这幅照片的曝光时间最接近( ) A．10－3 s B．10－6 s C．10－9 s D．10－12 s 7．下列说法中正确的是( ) A．变速直线运动的速度是变化的 B．平均速度即为一段时间内初末速度的平均值 C．瞬时速度是物体在某一时刻或在某一位置时的速度 D．瞬时速度可看作时间趋于无穷小时的平均速度 8．下列位移图象中，表示物体始终做匀速直线运动的是( ) A B C D 9．下列关于速度、加速度的描述中，正确的是( ) A．加速度在数值上等于单位时间内速度的变化量 B．物体的速度为零时，加速度也为零 C．物体的速度变化量越大，加速度越大 D．物体的速度变化越快，加速度越大 10．用打点计时器研究物体运动时，接通电源和让纸带随物体开始运动，这两个操作的时间关系应当是( ) A．先接通电源，后释放纸带B．先释放纸带，后接通电源 C．释放纸带的同时接通电源D．先释放纸带或先接通电源都可以 11．如图为某运动物体的速度—时间图象，下列说法中正确的是( ) A．物体以某初速开始运动，在0～2 s内加速运动，2～4 s内匀速运动，4～ 6 s内减速运动 5