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dc.contributor.authorJia, Bin
dc.contributor.authorSerra-Moreno, Ruth
dc.contributor.authorNeidermyer, William James
dc.contributor.authorRahmberg, Andrew
dc.contributor.authorMackey, John J.
dc.contributor.authorFofana, Ismael Farouck
dc.contributor.authorJohnson, Welkin Eric
dc.contributor.authorWestmoreland, Susan V.
dc.contributor.authorEvans, David T.
dc.date.accessioned2011-03-04T17:08:56Z
dc.date.issued2009
dc.identifier.citationJia, Bin, Ruth Serra-Moreno, William Neidermyer, Andrew Rahmberg, John Mackey, Ismael Ben Fofana, Welkin E. Johnson, Susan Westmoreland, and David T. Evans. 2009. Species-Specific Activity of SIV Nef and HIV-1 Vpu in Overcoming Restriction by Tetherin/BST2. PLoS Pathogens 5(5): e1000429.en_US
dc.identifier.issn1553-7366en_US
dc.identifier.urihttp://nrs.harvard.edu/urn-3:HUL.InstRepos:4737552
dc.description.abstractTetherin, also known as BST2, CD317 or HM1.24, was recently identified as an interferon-inducible host–cell factor that interferes with the detachment of virus particles from infected cells. HIV-1 overcomes this restriction by expressing an accessory protein, Vpu, which counteracts tetherin. Since lentiviruses of the SIVsmm/mac/HIV-2 lineage do not have a vpu gene, this activity has likely been assumed by other viral gene products. We found that deletion of the SIVmac239 nef gene significantly impaired virus release in cells expressing rhesus macaque tetherin. Virus release could be restored by expressing Nef in trans. However, Nef was unable to facilitate virus release in the presence of human tetherin. Conversely, Vpu enhanced virus release in the presence of human tetherin, but not in the presence of rhesus tetherin. In accordance with the species-specificity of Nef in mediating virus release, SIV Nef downregulated cell-surface expression of rhesus tetherin, but did not downregulate human tetherin. The specificity of SIV Nef for rhesus tetherin mapped to four amino acids in the cytoplasmic domain of the molecule that are missing from human tetherin, whereas the specificity of Vpu for human tetherin mapped to amino acid differences in the transmembrane domain. Nef alleles of SIVsmm, HIV-2 and HIV-1 were also able to rescue virus release in the presence of both rhesus macaque and sooty mangabey tetherin, but were generally ineffective against human tetherin. Thus, the ability of Nef to antagonize tetherin from these Old World primates appears to be conserved among the primate lentiviruses. These results identify Nef as the viral gene product of SIV that opposes restriction by tetherin in rhesus macaques and sooty mangabeys, and reveal species-specificity in the activities of both Nef and Vpu in overcoming tetherin in their respective hosts.en_US
dc.language.isoen_USen_US
dc.publisherPublic Library of Scienceen_US
dc.relation.isversionofdoi:10.1371/journal.ppat.1000429en_US
dc.relation.hasversionhttp://www.ncbi.nlm.nih.gov/pmc/articles/PMC2673686/pdf/en_US
dash.licenseLAA
dc.subjectvirologyen_US
dc.subjectanimal models of infectionen_US
dc.subjectimmune evasionen_US
dc.subjectimmunodeficiency virusesen_US
dc.subjectmechanisms of resistance and susceptibility, including host geneticsen_US
dc.subjectvirus evolution and symbiosisen_US
dc.titleSpecies-Specific Activity of SIV Nef and HIV-1 Vpu in Overcoming Restriction by Tetherin/BST2en_US
dc.typeJournal Articleen_US
dc.description.versionVersion of Recorden_US
dc.relation.journalPLoS Pathogensen_US
dash.depositing.authorSerra-Moreno, Ruth
dc.date.available2011-03-04T17:08:56Z
dash.affiliation.otherHMS^Microbiology and Molecular Geneticsen_US
dash.affiliation.otherHMS^New England Primate Research Centeren_US
dash.affiliation.otherHMS^Stipendees - Div of Medical Sciencesen_US
dash.affiliation.otherHMS^New England Primate Research Centeren_US
dash.affiliation.otherHMS^Microbiology and Molecular Geneticsen_US
dash.affiliation.otherHMS^Microbiology and Molecular Geneticsen_US
dash.affiliation.otherHMS^Pathologyen_US
dc.identifier.doi10.1371/journal.ppat.1000429*
dash.contributor.affiliatedNeidermyer, Bill
dash.contributor.affiliatedMackey, John
dash.contributor.affiliatedSerra-Moreno, Ruth
dash.contributor.affiliatedJia, Bin
dash.contributor.affiliatedEvans, David T.
dash.contributor.affiliatedFofana, Ismael Farouck
dash.contributor.affiliatedWestmoreland, Susan V.
dash.contributor.affiliatedJohnson, Welkin Eric


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