Dynamics of Glycoprotein Charge in the Evolutionary History of Human Influenza 英文参考文献.docVIP

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Dynamics of Glycoprotein Charge in the Evolutionary History of Human Influenza 英文参考文献.doc

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Dynamics of Glycoprotein Charge in the Evolutionary History of Human Influenza 英文参考文献

DynamicsofGlycoproteinChargeintheEvolutionary HistoryofHumanInfluenza NimalanArinaminpathy1*,BryanGrenfell1,2 1Department of Ecology and Evolutionary Biology, Princeton University, Princeton, New Jersey, United States of America, 2Fogarty International Center, National InstitutesofHealth,Bethesda,Maryland,UnitedStatesofAmerica Abstract Background:Influenzavirusesshowasignificantcapacitytoevadehostimmunity;thisismanifestbothaslargeoccasional jumpsintheantigenicphenotypeofviralsurfacemoleculesandingradualantigenicchangesleadingtoannualinfluenza epidemics in humans. Recent mouse studies show that avidity for host cells can play an important role in polyclonal antibodyescape,andfurtherthatelectrostaticchargeofthehemagglutininglycoproteincancontributetosuchavidity. Methodology/PrincipalFindings:Wetesttheroleofglycoproteinchargeonsequencedatafromthethreemajorsubtypes ofinfluenzaAinhumans,usingasimplemethodofcalculatingnetglycoproteincharge.Ofallsubtypes,H3N2inhumans shows a striking pattern of increasing positive charge since its introduction in 1968. Notably, this trend applies to both hemagglutinin and neuraminidase glycoproteins. In the late 1980s hemagglutinin charge reached a plateau, while neuraminidasechargestartedtodecline.Weidentifykeygroupsofaminoacidsitesinvolvedinthischargetrend. Conclusions/Significance:Toourknowledgethesearethefirstindicationsthat,forhumanH3N2,netglycoproteincharge covariesstronglywithantigenicdriftonaglobalscale.Furtherworkisneededtoelucidatehowsuchchargeinteractswith otherimmuneescapemechanisms,suchasglycosylation,andwediscussimportantquestionsarisingforfuturestudy. Citation: Arinaminpathy N, Grenfell B (2010) Dynamics of Glycoprotein Charge in the Evolutionary History of Human Influenza. PLoS ONE 5(12): e15674. doi:10.1371/journal.pone.0015674 Editor:Jean-PierreVartanian,InstitutPasteur,France ReceivedAugust2,2010;AcceptedNovember22,2010;PublishedDecember30,2010 Copyright: ? 2010 Arinaminpathy, Grenfell. This is an open-access article d