Mechanisms of GII.4 Norovirus Persistence in Human Populations 英文参考文献.docVIP

o PL SMEDICINE MechanismsofGII.4NorovirusPersistencein HumanPopulations Lisa C.Lindesmith1[,Eric F.Donaldson1[,Anna D.LoBue1,Jennifer L.Cannon1,2,Du-Ping Zheng2,Jan Vinje2, Ralph S.Baric1* 1UniversityofNorthCarolina-ChapelHill,ChapelHill,NorthCarolina,UnitedStatesofAmerica,2CentersforDiseaseControlandPrevention,Atlanta,Georgia,UnitedStates ofAmerica Funding:Thisworkwassupported byagrantfromtheNational InstitutesofHealth,Allergyand InfectiousDiseasesAI056351.The fundershadnoroleinstudydesign, datacollectionandanalysis,decision topublish,orpreparationofthe manuscript. ABSTRACT Background Norovirusesaretheleadingcauseofviralacutegastroenteritisinhumans,notedforcausing epidemic outbreaks in communities, the military, cruise ships, hospitals, and assisted living communities.Theevolutionarymechanismsgoverningthepersistenceandemergenceofnew norovirus strains in human populations are unknown. Primarily organized by sequence homologyintotwomajorhumangenogroupsdefinedbymultiplegenoclusters,themajority of norovirus outbreaks are caused by viruses from the GII.4 genocluster, which was first recognizedasthemajorepidemicstraininthemid-1990s.Previousstudiesbyourlaboratoryand othersindicatethatsome noroviruses readilyinfectindividuals whocarry a geneencodinga functionalalpha-1,2-fucosyltransferase(FUT2)andaredesignated‘‘secretor-positive’’toindicate thattheyexpressABHhisto-bloodgroupantigens(HBGAs),ahighlyheterogeneousgroupof relatedcarbohydratesonmucosalsurfaces.IndividualswithdefectsintheFUT2genearetermed secretor-negative,donotexpresstheappropriateHBGAnecessaryfordocking,andareresistant to Norwalk infection. These data argue that FUT2 and other genes encoding enzymes that regulate processing of the HBGA carbohydrates function as susceptibility alleles. However, secretor-negativeindividualscanbeinfectedwithothernorovirusstrains,andreinfectionwith the GII.4 strains is common in human populations. In this article, we analyze molecular mechanismsgoverningGII.4epidemiology,su