Murine Leukemia Virus Spreading in Mice Impaired in the Biogenesis of Secretory Lysosomes and Ca2+-Regulated Exocytosis 英文参考文献.docVIP

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Murine Leukemia Virus Spreading in Mice Impaired in the Biogenesis of Secretory Lysosomes and Ca2+-Regulated Exocytosis 英文参考文献.doc

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MurineLeukemiaVirusSpreadinginMiceImpairedintheBiogenesisofSecretoryLysosomesandCa2-RegulatedExocytosis英文参考文献

MurineLeukemiaVirusSpreadinginMiceImpairedin theBiogenesisofSecretoryLysosomesandCa - RegulatedExocytosis 2+ Wai-TsingChan1,NathanM.Sherer1¤,PradeepD.Uchil1,EdwardK.Novak2,RichardT.Swank2 ,Walther Mothes1* 1Section of Microbial Pathogenesis, Yale University School of Medicine, New Haven, Connecticut, United States of America, 2Department of Molecular and Cellular Biology,RoswellParkCancerInstitute,Buffalo,NewYork,UnitedStatesofAmerica Abstract Background: Retroviruses have beenobserved to bud intracellularly into multivesicular bodies (MVB), in addition to the plasmamembrane.ReleasefromMVBisthoughttooccurbyCa -regulatedfusionwiththeplasmamembrane. 2+ Principal Findings: To address the role of the MVB pathway in replication of the murine leukemia virus (MLV) we took advantageofmousemodelsfortheHermansky-Pudlaksyndrome(HPS)andGriscellisyndrome.Inhumans,thesedisordersare characterizedbyhypopigmentationandimmunologicalalterationsthatarecausedbydefectsinthebiogenesisandtrafficking ofMVBsandotherlysosomerelatedorganelles.NeonatalmiceforthesediseasemodelslackingfunctionalAP-3,Rab27Aand BLOCfactorswereinfectedwithMoloneyMLVandthespreadofvirusintobonemarrow,spleenandthymuswasmonitored. WefoundamoderatereductioninMLVinfectionlevelsinmostmutantmice,whichdifferedbylessthantwo-foldcomparedto wild-typemice.Invitro,MLVreleaseformbone-marrowderivedmacrophageswasslightlyenhanced.Finally,wefoundno 2+ evidenceforaCa -regulatedreleasepathwayinvitro.Furthermore,MLVreplicationwasonlymoderatelyaffectedinmice lackingSynaptotagminVII,aCa -sensorregulatinglysosomefusionwiththeplasmamembrane. 2+ Conclusions:GiventhatMLVspreadinginmicedependsonmultipleroundsofreplicationevenmoderatereductionofvirus releaseatthecellularlevelwouldaccumulateandleadtoasignificanteffectovertime.Thusourinvivoandinvitrodata collectivelyargueagainstanessentialroleforaMVB-andsecretorylysosome-mediatedpathwayintheegressofMLV. Citation:ChanWT,ShererNM,UchilPD,NovakEK,SwankRT,etal.(2008)MurineLeukemiaVirusSp