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dc.contributor.authorGroppelli, Elisabettaen_US
dc.contributor.authorLevy, Hazel C.en_US
dc.contributor.authorSun, Eileenen_US
dc.contributor.authorStrauss, Mikeen_US
dc.contributor.authorNicol, Clareen_US
dc.contributor.authorGold, Sarahen_US
dc.contributor.authorZhuang, Xiaoweien_US
dc.contributor.authorTuthill, Tobias J.en_US
dc.contributor.authorHogle, James M.en_US
dc.contributor.authorRowlands, David J.en_US
dc.date.accessioned2017-04-06T03:19:49Z
dc.date.issued2017en_US
dc.identifier.citationGroppelli, Elisabetta, Hazel C. Levy, Eileen Sun, Mike Strauss, Clare Nicol, Sarah Gold, Xiaowei Zhuang, Tobias J. Tuthill, James M. Hogle, and David J. Rowlands. 2017. “Picornavirus RNA is protected from cleavage by ribonuclease during virion uncoating and transfer across cellular and model membranes.” PLoS Pathogens 13 (2): e1006197. doi:10.1371/journal.ppat.1006197. http://dx.doi.org/10.1371/journal.ppat.1006197.en
dc.identifier.issnen
dc.identifier.urihttp://nrs.harvard.edu/urn-3:HUL.InstRepos:32072122
dc.description.abstractPicornaviruses are non-enveloped RNA viruses that enter cells via receptor-mediated endocytosis. Because they lack an envelope, picornaviruses face the challenge of delivering their RNA genomes across the membrane of the endocytic vesicle into the cytoplasm to initiate infection. Currently, the mechanism of genome release and translocation across membranes remains poorly understood. Within the enterovirus genus, poliovirus, rhinovirus 2, and rhinovirus 16 have been proposed to release their genomes across intact endosomal membranes through virally induced pores, whereas one study has proposed that rhinovirus 14 releases its RNA following disruption of endosomal membranes. For the more distantly related aphthovirus genus (e.g. foot-and-mouth disease viruses and equine rhinitis A virus) acidification of endosomes results in the disassembly of the virion into pentamers and in the release of the viral RNA into the lumen of the endosome, but no details have been elucidated as how the RNA crosses the vesicle membrane. However, more recent studies suggest aphthovirus RNA is released from intact particles and the dissociation to pentamers may be a late event. In this study we have investigated the RNase A sensitivity of genome translocation of poliovirus using a receptor-decorated-liposome model and the sensitivity of infection of poliovirus and equine-rhinitis A virus to co-internalized RNase A. We show that poliovirus genome translocation is insensitive to RNase A and results in little or no release into the medium in the liposome model. We also show that infectivity is not reduced by co-internalized RNase A for poliovirus and equine rhinitis A virus. Additionally, we show that all poliovirus genomes that are internalized into cells, not just those resulting in infection, are protected from RNase A. These results support a finely coordinated, directional model of viral RNA delivery that involves viral proteins and cellular membranes.en
dc.language.isoen_USen
dc.publisherPublic Library of Scienceen
dc.relation.isversionofdoi:10.1371/journal.ppat.1006197en
dc.relation.hasversionhttp://www.ncbi.nlm.nih.gov/pmc/articles/PMC5325612/pdf/en
dash.licenseLAAen_US
dc.subjectBiology and life sciencesen
dc.subjectBiochemistryen
dc.subjectProteinsen
dc.subjectDNA-binding proteinsen
dc.subjectNucleasesen
dc.subjectRibonucleasesen
dc.subjectBiology and Life Sciencesen
dc.subjectEnzymologyen
dc.subjectEnzymesen
dc.subjectHydrolasesen
dc.subjectOrganismsen
dc.subjectVirusesen
dc.subjectRNA virusesen
dc.subjectCell Biologyen
dc.subjectCellular Structures and Organellesen
dc.subjectVesiclesen
dc.subjectLiposomesen
dc.subjectExtraction techniquesen
dc.subjectRNA extractionen
dc.subjectCytoplasmen
dc.subjectImaging Techniquesen
dc.subjectFluorescence Imagingen
dc.subjectSignal Transductionen
dc.subjectCell Signalingen
dc.subjectMembrane Receptor Signalingen
dc.titlePicornavirus RNA is protected from cleavage by ribonuclease during virion uncoating and transfer across cellular and model membranesen
dc.typeJournal Articleen_US
dc.description.versionVersion of Recorden
dc.relation.journalPLoS Pathogensen
dash.depositing.authorZhuang, Xiaoweien_US
dc.date.available2017-04-06T03:19:49Z
dc.identifier.doi10.1371/journal.ppat.1006197*
dash.contributor.affiliatedHogle, James
dash.contributor.affiliatedZhuang, Xiaowei


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