冠状病毒Coronavirusl论文-2007 Human Immunodeficiency Viral Vector Pseudotyped with the Spike Envelope of Severe Acute Respiratory Syndrome Corona.pdf

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1、HUMANGENETHERAPY18:413–422(May2007)©MaryAnnLiebert,Inc.DOI:10.1089/hum.2006.194HumanImmunodeficiencyViralVectorPseudotypedwiththeSpikeEnvelopeofSevereAcuteRespiratorySyndromeCoronavirusTransducesHumanAirwayEpithelialCellsandDendriticCellsGARYP.KOBINGER,1,2MARIAP.LIMBERIS,3SURISOMANATHAN,3GREGORY

2、SCHUMER,4PETERBELL,3andJAMESM.WILSON3ABSTRACTThehumansevereacuterespiratorysyndromecoronavirus(SARS-CoV)isahighlyinfectiousvirusthatcausessevererespiratoryinfectionsinhumans.ThespikeenvelopeglycoproteinofSARS-CoV,themaindetermi-nantofSARS-CoVtropism,wasisolatedandusedtopseudotypeahumanimmunodefi

3、ciencyvirus(HIV)-basedvector.Spike-pseudotypedHIVvectorwasgeneratedandevaluatedinvitroonwell-differentiatedhu-manairwayepithelialcellsandbronchialexplantsandinvivoinmurineairways.ThespikeenvelopewaslessefficientatpromotingHIVvectortransductionofmurineairwayepitheliumthananoptimizeddeletionmu-tan

4、toftheZaireebolavirusenvelopeglycoprotein(NTD6L),whichwasusedasabenchmark.However,spike-pseudotypedHIVvectorwassubstantiallymoreefficientthanNTD6L-pseudotypedvectoronhumanairwayepitheliumasdemonstratedbylacZgenetransferinprimaryculturesofepithelialcellsandbronchialex-plants.Inaddition,thisstudys

5、howsthatspike-pseudotypedHIV-basedvectorcanefficientlytransducehu-mandendriticcellsandepithelialcellsoftheesophagus,whichmayhaveimplicationsininvestigatingmech-anismsofSARS-CoVpathogenesis.Spike-pseudotypedHIV-basedvectorisanovellung-directedgenetransfervehiclethatholdspromiseforthetreatmentofge

6、neticlungdiseasessuchascysticfibrosisor1-antitrypsindeficiency.INTRODUCTIONtheenvelopeglycoproteinoftheZaireebolaviruscansuccess-fullypseudotypeHIV-basedvectorsandpromoteefficientgeneENTIVIRALVECTORScanbeefficientlypseudotypedwithen-transfertoairwayepitheliaandsubmucosalglandsinvivo(Kob-Lvelope

7、proteinsfrommanyvirusesincludingtheglyco-ingeretal.,2001;Medinaetal.,2003).Additionaldevelop-proteinfromvesicularstomatitisvirus(VSV-G)(Naldinietal.,mentoftheZaireebolavirusledtothegenerationoftwoopti-1996).AlthoughVSV-G-pse