ZAP和MHV-68相互作用的机理研究-豆柴文库

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ZAP和MHV-68相互作用的机理研究
引言
Herpesvirusfamilyincludesseveralhumanviralpathogenssuchasherpessimplexvirus(HSV),Epstein-Barrvirus(EBV)andcytomegalovirus(CMV).Murineherpesvirus-68(MHV-68)isaγ-herpesviruswhichservesasamodelforstudyinghumanγ-herpesviruses.Theimmediateearlygenetranscriptionfactor,ZtaActivationProtein(ZAP),isanimportantregulatorofgeneexpressionforbothHSV-1andMHV-68.ZAPisknowntointeractwithseveralvirusesincludingretroviruses,alphaviruses,filoviruses,andflaviviruses.Inthisarticle,wewillreviewthemechanismsbywhichZAPinteractswithMHV-68andtheconsequencesofthisinteractiononthevirusreplicationcycle.
ZAPandMHV-68
ZAPisazincfingerantiviralproteinthatplaysacriticalroleininnateimmunity.ItsexpressionisinducedbytypeIinterferons,whichstimulatethetranscriptionandtranslationoftheZAPgene.ZAPbindstoviralRNAandrecruitscellularRNAdegradationmachinerytoinduceRNAdegradation,leadingtoinhibitionofviralreplication.ZAPhasbeenshowntobeaneffectiveinhibitorofseveralRNAviruses;however,itsimpactonDNAvirusesislessclear.
MHV-68isaDNAvirusthatinfectsbothmouseandhumancells.ThevirusisknowntoestablishalatentinfectionwithinB-cells,whichcanleadtooncogenesis.AscreenforproteinsthatinteractwithMHV-68revealedthatZAPbindstotheimmediateearlygene,Rta,whichisessentialfortheviruslyticreplicationcycle.TheinteractionbetweenZAPandRtawasfoundtobedirectandspecific,asdemonstratedbyco-immunoprecipitationexperiments.
ThedirectinteractionbetweenZAPandRtasuggeststhatZAPmayplayaroleinregulatingtheexpressionofviralgenesduringthelyticphaseofMHV-68replication.Indeed,ZAPwasfoundtoinhibitMHV-68replicationinbothprimarymouseembryonicfibroblastsandhumanembryonickidneycells.TheinhibitoryeffectofZAPonMHV-68replicationwasdependentonthepresenceofbothZAPandRta,suggestingthatZAPmayregulateRtafunctionsduringtheearlyphasesofthelyticreplicationcycle.
ConsequencesofZAPandMHV-68Interaction
Inadditiontoitsroleinregulatingviralreplication,ZAPhasbeenshowntoinduceapoptoticcelldeathininfectedcells.Therefore,itispossiblethatZAPmayserveasacritic