冠狀病毒Coronavirusl論文-2012 [Advances in Experimental Medicine and Biology] The Effects of Noise on Aquatic Life Volume 730 __ Molecular Analys.pdf

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1、8MOLECULARANALYSISOFTHECORONAVIRUS-RECEPTORFUNCTIONOFAMINOPEPTIDASENAndreasF.Kolb,AnnetteHegyi,JuliaMaile,AngelienHeister,MargittaHagemann,andStuartG.SiddellInstituteofVirologyandImmunologyUniversityofWiirzburg,Versbacherstr.7D-97078Wiirzburg,Germany1.ABSTRACTAminopeptidaseN(A

2、PN)isamajorcellsurfaceforcoronavirusesoftheserogroupI.ByusingchimericAPNproteinsassembledfromhuman,porcineandfelineAPNwehaveidentifieddeterminantswhicharecriticallyinvolvedinthecoronavirus-APNinterac?tion.Ourresultsindicatethathumancoronavirus229E(HCV229E)isdistinctfromtheothe

3、rserogroupIcoronavirusesinthatdeterminantslocatedwithintheN-terminalpartsofthehumanandfelineAPNproteinsmediatetheinfectionofHCV229E,whereasdetermi?nantslocatedwithintheC-terminalpartsofporcine,felineandcanineAPNmediatetheinfectionoftransmissiblegastro-enteritisvirus(TGEV),feli

4、neinfectiousperitonitisvirus(FIPV)andcaninecoronavirus(CCV),respectively.Afurtheranalysisofthemappedaminoacidsegmentsbysitedirectedmutagenesisrevealedthatashortstretchof8aminoacidsinthehAPNproteinplaysadecisiveroleinmediatingHCV229Ereception.2.INTRODUCTIONOnthebasisofserologic

5、alandgeneticaldata,coronavirusesareclassifiedintothreedifferentserogroups(Siddell,1995).ThemembersofserogroupIutilisethecellsurfacemoleculeaminopeptidaseN(APN)asareceptor(DelmasetaI.,1992;YeageretaI.,1992;TresnanetaI.,1996).HumanAPNandporcineAPNactspeciesspecificallyinthatthey

6、onlymediatetheinfectionofthehumancoronavirus229EandtheporcinecoronavirusTGEV,respectively(DelmasetaI.,1994;KolbetaI.,1996).Incontrast,thefelineAPNproteinisabletomediateinfectionofFIPV,TGEV,HCV229EandCCV(TresnanetaI.,CoronavirusesandArteriviruses,editedbyEnjuanesetat.PlenumPres

7、s,NewYork,19986162A.F.Kolbetaf.1996).However,thefelinecoronavirusFIPVcanonlyutilisefAPNasareceptor.Byus?ingchimericmoleculesassembledfromhAPNandpAPNthedeterminantswhichplayanessentialroleintheinfectionofHCV229EandTGEVhavebeenidentified(Delmaseta!.,1994;Kolbeta!.,1996).Theregio

8、nencompassingpAPNaminoacids717-813hasbeendelimitedastheprotei