A Large and Intact Viral Particle Penetrates the Endoplasmic Reticulum Membrane to Reach the Cytosol 英文参考文献.docVIP

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A Large and Intact Viral Particle Penetrates the Endoplasmic Reticulum Membrane to Reach the Cytosol 英文参考文献.doc

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A Large and Intact Viral Particle Penetrates the Endoplasmic Reticulum Membrane to Reach the Cytosol 英文参考文献

ALargeandIntactViralParticlePenetratesthe EndoplasmicReticulumMembranetoReachtheCytosol TakamasaInoue,BillyTsai* DepartmentofCellandDevelopmentalBiology,UniversityofMichiganMedicalSchool,AnnArbor,Michigan,UnitedStatesofAmerica Abstract Non-envelopedvirusespenetratehostmembranestoinfectcells.Acell-basedassaywasusedtoprobetheendoplasmic reticulum(ER)-to-cytosolmembranetransportofthenon-envelopedSV40.Wefoundthat,uponERarrival,SV40isreleased into the lumen and undergoes sequential disulfide bond disruptions to reach the cytosol. However, despite these ER- dependentconformationalchanges,SV40crossestheERmembraneasalargeandintactparticleconsistingoftheVP1coat, theinternalcomponentsVP2,VP3,andthegenome.Thislargeparticlesubsequentlydisassemblesinthecytosol.Mutant virusandinhibitorstudiesdemonstrateVP3andlikelytheviralgenome,aswellascellularproteasome,controlER-to-cytosol transport.Ourresultsidentifythesequenceofevents,aswellasvirusandhostcomponents,thatregulateERmembrane penetration. They also suggest that the ER membrane supports passage of a large particle, potentially through either a sizeableprotein-conductingchannelorthelipidbilayer. Citation: Inoue T, Tsai B (2011) A Large and Intact Viral Particle Penetrates the Endoplasmic Reticulum Membrane to Reach the Cytosol. PLoS Pathog 7(5): e1002037.doi:10.1371/journal.ppat.1002037 Editor:DeniseGalloway,FredHutchinsonCancerResearchCenter,UnitedStatesofAmerica ReceivedOctober10,2010;AcceptedMarch7,2011;PublishedMay12,2011 Copyright: ? 2011 Inoue, Tsai. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricteduse,distribution,andreproductioninanymedium,providedtheoriginalauthorandsourcearecredited. Funding:SupportwasprovidedbytheNIH/NIAIDgrantAI064296(BT).Thefundershadnoroleinstudydesign,datacollectionandanalysis,decisiontopublish, orpreparationofthemanuscript. CompetingInterests:Theauthorshavedeclaredthatnocompetinginterestsexist. *E-mail:btsai@ Introduc