Analysis of Amino Acid Variation in the P2 Domain of the GII-4 Norovirus VP1 Protein Reveals Putative Variant-Specific Epitopes 英文参考文献.docVIP
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Analysis of Amino Acid Variation in the P2 Domain of the GII-4 Norovirus VP1 Protein Reveals Putative Variant-Specific Epitopes 英文参考文献
AnalysisofAminoAcidVariationintheP2Domainofthe
GII-4NorovirusVP1ProteinRevealsPutativeVariant-
SpecificEpitopes
DavidJ.Allen1,2*,JimJ.Gray1,ChrisI.Gallimore1,JacquelineXerry1,MirenIturriza-Go′mara1
1Enteric Virus Unit, Virus Reference Department, Centre For Infections, Health Protection Agency, London, United Kingdom, 2Department of
InfectiousandTropicalDiseases,LondonSchoolofHygieneandTropicalMedicine,London,UnitedKingdom
Background.Humannorovirusesareahighlydiversegroupofvirusesclassifiedintothreeofthefivecurrentlyrecognised
Norovirusgenogroups,andcontainnumerousgenotypesorgeneticclusters.Norovirusesarethemajoraetiologicalagentof
endemic gastroenteritis in all age groups, as well as the cause of periodic epidemic gastroenteritis. The noroviruses most
commonlyassociatedwithoutbreaksofgastroenteritisaregenogroupIIgenotype4(GII-4)strains.Therelationshipbetween
genotypes of noroviruses with their phenotypes and antigenic profile remains poorly understood through an inability to
culturethesevirusesandthelackofasuitableanimalmodel.Methodology/PrincipalFindings.Herewedescribeastudyof
thediversityofaminoacidsequencesofthehighlyvariableP2regioninthemajorcapsidprotein,VP1,oftheGII-4human
noroviruses strains using sequence analysis and homology modelling techniques. Conclusions/Significance. Our data
identifiestwositesinthisregion,whichshowsignificantaminoacidsubstitutionsassociatedwiththeappearanceofvariant
strainsresponsibleforepidemicswithmajorpublichealthimpact.Homologymodellingstudiesrevealedtheexposednature
ofthesesitesonthecapsidsurface,providingsupportivestructuraldatathatthesetwositesarelikelytobeassociatedwith
putative variant-specific epitopes. Furthermore, the patterns in the evolution of these viruses at these sites suggests that
norovirusesfollowaneutralnetworkpatternofevolution.
Citation: AllenDJ,GrayJJ,GallimoreCI,XerryJ,Iturriza-Go′maraM(2008)AnalysisofAminoAcidVariationintheP2DomainoftheGII-4Norovirus
VP1ProteinRevealsPutativeVariant-SpecificEpitopes.PLoS
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