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1、REVIEWSCoronavirusespost-SARS:updateonreplicationandpathogenesisStanleyPerlmanandJasonNetlandAbstract

2、Althoughcoronaviruseswerefirstidentifiednearly60yearsago,theyonlyreceivednotorietyin2003whenoneoftheirmemberswasidentifiedastheaetiologicalagentofsevereacuterespiratorysynd

3、rome.Previouslytheseviruseswereknowntobeimportantagentsofrespiratoryandentericinfectionsofdomesticandcompanionanimalsandtocauseapproximately15%ofallcasesofthecommoncold.ThisReviewfocusesonrecentadvancesinourunderstandingofthemechanismsofcoronavirusreplication,interactionswi

4、ththehostimmuneresponseanddiseasepathogenesis.Italsohighlightstherecentidentificationofnumerousnovelcoronavirusesandthepropensityofthisvirusfamilytocrossspeciesbarriers.Coronaviruses,agenusintheCoronaviridaefamily(orderencodeanadditionalhaemagglutinin-esterase(HE)pro-Prothr

5、ombinaseMoleculethatcleavesNidovirales;fig.1),arepleomorphic,envelopedviruses.tein(fig.2a,b).TheHEprotein,whichmaybeinvolvedthrombin,therebyinitiatingtheCoronavirusesgainedprominenceduringthesevereacuteinvirusentryoregress,isnotrequiredforreplica-coagulationcascade.respirat

6、orysyndrome(SARS)outbreaksof2002–2003tion,butappearstobeimportantforinfectionofthe(ref.1).Theviralmembranecontainsthetransmembranenaturalhost5.(M)glycoprotein,thespike(S)glycoproteinandtheenve-Receptorsforseveralcoronaviruseshavebeeniden-lope(E)protein,andsurroundsadisorder

7、edorflexible,tified(TABLe1).Theprototypicalcoronavirus,mouseprobablyhelical,nucleocapsid2,3.Theviralmembraneishepatitisvirus(MHV),usesCEACAM1a,amemberofunusuallythick,probablybecausethecarboxy-terminalthemurinecarcinoembryonicantigenfamily,toenterregionoftheMproteinformsane

8、xtrainternallayer,ascells.Deletionofthisproteinmakesmiceresistanttorevealedbycryo-electrontomography2.Coronavirusesinfection6.Severalgroup1coronavirusesuseami-aredividedintothreegroups,andfurthersubdividednopeptidaseNtoadheretohostcells,consistentwithintosubgroups(TABLe1),b

9、asedinitiallyonserologic,andtheirrespiratoryandenterictracttropisms(reviewedinmore