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dc.contributor.authorWu, Fan
dc.contributor.authorNewman, Ruchi M.
dc.contributor.authorO'Connor, Shelby
dc.contributor.authorMarx, Preston A.
dc.contributor.authorGoldstein, Simoy
dc.contributor.authorBuckler-White, Alicia
dc.contributor.authorHirsch, Vanessa M.
dc.contributor.authorKirmaier, Andrea
dc.contributor.authorHall, Laura R
dc.contributor.authorMorgan, Jennifer Sauvron
dc.contributor.authorMeythaler, Mareike
dc.contributor.authorKaur, Amitinder
dc.contributor.authorJohnson, Welkin Eric
dc.date.accessioned2011-11-24T02:59:48Z
dc.date.issued2010
dc.identifier.citationKirmaier, Andrea, Fan Wu, Ruchi M. Newman, Laura R. Hall, Jennifer S. Morgan, Shelby O'Connor, Preston A. Marx, et al. 2010. TRIM5 Suppresses Cross-Species Transmission of a Primate Immunodeficiency Virus and Selects for Emergence of Resistant Variants in the New Species. PLoS Biology 8(8): e1000462.en_US
dc.identifier.issn1544-9173en_US
dc.identifier.urihttp://nrs.harvard.edu/urn-3:HUL.InstRepos:5352092
dc.description.abstractSimian immunodeficiency viruses of sooty mangabeys (SIVsm) are the source of multiple, successful cross-species transmissions, having given rise to HIV-2 in humans, SIVmac in rhesus macaques, and SIVstm in stump-tailed macaques. Cellular assays and phylogenetic comparisons indirectly support a role for TRIM5a, the product of the TRIM5 gene, in suppressing interspecies transmission and emergence of retroviruses in nature. Here, we investigate the in vivo role of TRIM5 directly, focusing on transmission of primate immunodeficiency viruses between outbred primate hosts. Specifically, we retrospectively analyzed experimental cross-species transmission of SIVsm in two cohorts of rhesus macaques and found a significant effect of TRIM5 genotype on viral replication levels. The effect was especially pronounced in a cohort of animals infected with SIVsmE543-3, where TRIM5 genotype correlated with approximately 100-fold to 1,000-fold differences in viral replication levels. Surprisingly, transmission occurred even in individuals bearing restrictive TRIM5 genotypes, resulting in attenuation of replication rather than an outright block to infection. In cell-culture assays, the same TRIM5 alleles associated with viral suppression in vivo blocked infectivity of two SIVsm strains, but not the macaque-adapted strain SIVmac239. Adaptations appeared in the viral capsid in animals with restrictive TRIM5 genotypes, and similar adaptations coincide with emergence of SIVmac in captive macaques in the 1970s. Thus, host TRIM5 can suppress viral replication in vivo, exerting selective pressure during the initial stages of cross-species transmission.en_US
dc.language.isoen_USen_US
dc.publisherPublic Library of Scienceen_US
dc.relation.isversionofdoi:10.1371/journal.pbio.1000462en_US
dc.relation.hasversionhttp://www.ncbi.nlm.nih.gov/pmc/articles/PMC2927514/pdf/en_US
dash.licenseLAA
dc.subjectvirologyen_US
dc.subjectanimal models of infectionen_US
dc.subjectimmunodeficiency virusesen_US
dc.subjectmechanisms of resistance and susceptibility, including host geneticsen_US
dc.subjectvirus evolution and symbiosisen_US
dc.titleTRIM5 Suppresses Cross-Species Transmission of a Primate Immunodeficiency Virus and Selects for Emergence of Resistant Variants in the New Speciesen_US
dc.typeJournal Articleen_US
dc.description.versionVersion of Recorden_US
dc.relation.journalPLoS Biologyen_US
dash.depositing.authorKirmaier, Andrea
dc.date.available2011-11-24T02:59:48Z
dash.affiliation.otherHMS^Microbiology and Molecular Geneticsen_US
dash.affiliation.otherHMS^Microbiology and Molecular Geneticsen_US
dc.identifier.doi10.1371/journal.pbio.1000462*
dash.authorsorderedfalse
dash.contributor.affiliatedMorgan, Jennifer Sauvron
dash.contributor.affiliatedKaur, Amitinder
dash.contributor.affiliatedKirmaier, Andrea
dash.contributor.affiliatedHall, Laura R
dash.contributor.affiliatedJohnson, Welkin Eric


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