Please use this identifier to cite or link to this item: http://hdl.handle.net/2381/26367
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dc.contributor.authorWain, LV-
dc.contributor.authorBailes, E-
dc.contributor.authorBibollet-Ruche, F-
dc.contributor.authorDecker, JM-
dc.contributor.authorKeele, BF-
dc.contributor.authorVan Heuverswyn F-
dc.contributor.authorLi, Y-
dc.contributor.authorTakehisa, J-
dc.contributor.authorNgole, EM-
dc.contributor.authorShaw, GM-
dc.contributor.authorPeeters, M-
dc.contributor.authorHahn, BH-
dc.contributor.authorSharp, PM-
dc.date.accessioned2012-10-24T09:21:39Z-
dc.date.available2012-10-24T09:21:39Z-
dc.date.issued2007-08-
dc.identifier.citationMOL BIOL EVOL, 2007, 24 (8), pp. 1853-1860-
dc.identifier.issn0737-4038-
dc.identifier.urihttp://hdl.handle.net/2381/26367-
dc.description.abstractHuman immunodeficiency virus type 1 (HIV-1) originated from three independent cross-species transmissions of simian immunodeficiency virus (SIVcpzPtt) infecting chimpanzees (Pan troglodytes troglodytes) in west central Africa, giving rise to pandemic (group M) and non-pandemic (groups N and O) clades of HIV-1. To identify host-specific adaptations in HIV-1 we compared the inferred ancestral sequences of HIV-1 groups M, N and O to 12 full length genome sequences of SIVcpzPtt and four of the outlying but closely related SIVcpzPts (from P. t. schweinfurthii). This analysis revealed a single site that was completely conserved among SIVcpzPtt strains but different (due to the same change) in all three groups of HIV-1. This site, Gag-30, lies within p17, the gag-encoded matrix protein. It is Met in SIVcpzPtt, underwent a conservative replacement by Leu in one lineage of SIVcpzPts but changed radically to Arg on all three lineages leading to HIV-1. During subsequent diversification this site has been conserved as a basic residue (Arg or Lys) in most lineages of HIV-1. Retrospective analysis revealed that Gag-30 had reverted to Met in a previous experiment in which HIV-1 was passaged through chimpanzees. To examine whether this substitution conferred a species specific growth advantage, we used site-directed mutagenesis to generate variants of these chimpanzee-adapted HIV-1 strains with Lys at Gag-30, and tested their replication in both human and chimpanzee CD4+ T lymphocytes. Remarkably, viruses encoding Met replicated to higher titers than viruses encoding Lys in chimpanzee T cells, but the opposite was found in human T cells. Taken together, these observations provide compelling evidence for host-specific adaptation during the emergence of HIV-1 and identify the viral matrix protein as a modulator of viral fitness following transmission to the new human host.-
dc.formatmetadata-
dc.language.isoeng-
dc.sourcePubMed-
dc.source.urihttp://www.ncbi.nlm.nih.gov/pubmed/-
dc.subjectAcquired Immunodeficiency Syndrome-
dc.subjectAfrica-
dc.subjectCentral-
dc.subjectAnimals-
dc.subjectBiological Evolution-
dc.subjectCD4-Positive T-Lymphocytes-
dc.subjectGene Products-
dc.subjectgag-
dc.subjectHIV-1-
dc.subjectHumans-
dc.subjectMutagenesis-
dc.subjectSite-Directed-
dc.subjectMutation-
dc.subjectPan troglodytes-
dc.subjectPhylogeny-
dc.subjectSequence Analysis-
dc.subjectDNA-
dc.subjectSimian Acquired Immunodeficiency Syndrome-
dc.subjectSimian immunodeficiency virus-
dc.subjectVirus Replication-
dc.titleAdaptation of HIV-1 to its human host.-
dc.typeJournal Article-
dc.identifier.doi10.1093/molbev/msm110-
dc.identifier.piimsm110-
dc.description.irispid91152-
Appears in Collections:Published Articles, Dept. of Health Sciences

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