Adaptation of HIV-1 to Its Human Host
Human 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) clade...
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creator | Wain, Louise V. Bailes, Elizabeth Bibollet-Ruche, Frederic Decker, Julie M. Keele, Brandon F. Van Heuverswyn, Fran Li, Yingying Takehisa, Jun Ngole, Eitel Mpoudi Shaw, George M. Peeters, Martine Hahn, Beatrice H. Sharp, Paul M. |
description | Human 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. |
doi_str_mv | 10.1093/molbev/msm110 |
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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.</description><identifier>ISSN: 0737-4038</identifier><identifier>EISSN: 1537-1719</identifier><identifier>DOI: 10.1093/molbev/msm110</identifier><identifier>PMID: 17545188</identifier><language>eng</language><publisher>United States: Oxford University Press</publisher><subject>Acquired Immunodeficiency Syndrome - epidemiology ; Acquired Immunodeficiency Syndrome - transmission ; Acquired Immunodeficiency Syndrome - virology ; Adaptation ; Africa, Central ; Animals ; Biological Evolution ; CD4-Positive T-Lymphocytes - metabolism ; CD4-Positive T-Lymphocytes - virology ; Evolutionary biology ; Gene Products, gag - genetics ; Gene Products, gag - metabolism ; Genomics ; HIV ; HIV-1 - physiology ; Human immunodeficiency virus ; Human immunodeficiency virus 1 ; Humans ; Lymphocytes ; Molecular biology ; Mutagenesis, Site-Directed ; Mutation - genetics ; Pan troglodytes ; Pan troglodytes troglodytes ; Pandemics ; Phylogeny ; Primates ; Sequence Analysis, DNA ; Simian Acquired Immunodeficiency Syndrome - epidemiology ; Simian Acquired Immunodeficiency Syndrome - transmission ; Simian Acquired Immunodeficiency Syndrome - virology ; Simian immunodeficiency virus ; Simian Immunodeficiency Virus - classification ; Simian Immunodeficiency Virus - genetics ; Simian Immunodeficiency Virus - isolation & purification ; Virus Replication</subject><ispartof>Molecular biology and evolution, 2007-08, Vol.24 (8), p.1853-1860</ispartof><rights>The Author 2007. Published by Oxford University Press on behalf of the Society for Molecular Biology and Evolution. All rights reserved. For permissions, please e-mail: journals.permissions@oxfordjournals.org 2007</rights><rights>The Author 2007. Published by Oxford University Press on behalf of the Society for Molecular Biology and Evolution. All rights reserved. For permissions, please e-mail: journals.permissions@oxfordjournals.org</rights><rights>The Author 2007. Published by Oxford University Press on behalf of the Society for Molecular Biology and Evolution. All rights reserved. 2007</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c476t-e94a70e0edc3599fdd509ceb8a72fa4175ee46f17963f0ab57a95f26b3b185933</citedby><cites>FETCH-LOGICAL-c476t-e94a70e0edc3599fdd509ceb8a72fa4175ee46f17963f0ab57a95f26b3b185933</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>230,314,780,784,885,1603,27922,27923</link.rule.ids><linktorsrc>$$Uhttps://dx.doi.org/10.1093/molbev/msm110$$EView_record_in_Oxford_University_Press$$FView_record_in_$$GOxford_University_Press</linktorsrc><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/17545188$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Wain, Louise V.</creatorcontrib><creatorcontrib>Bailes, Elizabeth</creatorcontrib><creatorcontrib>Bibollet-Ruche, Frederic</creatorcontrib><creatorcontrib>Decker, Julie M.</creatorcontrib><creatorcontrib>Keele, Brandon F.</creatorcontrib><creatorcontrib>Van Heuverswyn, Fran</creatorcontrib><creatorcontrib>Li, Yingying</creatorcontrib><creatorcontrib>Takehisa, Jun</creatorcontrib><creatorcontrib>Ngole, Eitel Mpoudi</creatorcontrib><creatorcontrib>Shaw, George M.</creatorcontrib><creatorcontrib>Peeters, Martine</creatorcontrib><creatorcontrib>Hahn, Beatrice H.</creatorcontrib><creatorcontrib>Sharp, Paul M.</creatorcontrib><title>Adaptation of HIV-1 to Its Human Host</title><title>Molecular biology and evolution</title><addtitle>Mol Biol Evol</addtitle><description>Human 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.</description><subject>Acquired Immunodeficiency Syndrome - epidemiology</subject><subject>Acquired Immunodeficiency Syndrome - transmission</subject><subject>Acquired Immunodeficiency Syndrome - virology</subject><subject>Adaptation</subject><subject>Africa, Central</subject><subject>Animals</subject><subject>Biological Evolution</subject><subject>CD4-Positive T-Lymphocytes - metabolism</subject><subject>CD4-Positive T-Lymphocytes - virology</subject><subject>Evolutionary biology</subject><subject>Gene Products, gag - genetics</subject><subject>Gene Products, gag - metabolism</subject><subject>Genomics</subject><subject>HIV</subject><subject>HIV-1 - physiology</subject><subject>Human immunodeficiency virus</subject><subject>Human immunodeficiency virus 1</subject><subject>Humans</subject><subject>Lymphocytes</subject><subject>Molecular biology</subject><subject>Mutagenesis, Site-Directed</subject><subject>Mutation - genetics</subject><subject>Pan troglodytes</subject><subject>Pan troglodytes troglodytes</subject><subject>Pandemics</subject><subject>Phylogeny</subject><subject>Primates</subject><subject>Sequence Analysis, DNA</subject><subject>Simian Acquired Immunodeficiency Syndrome - epidemiology</subject><subject>Simian Acquired Immunodeficiency Syndrome - transmission</subject><subject>Simian Acquired Immunodeficiency Syndrome - virology</subject><subject>Simian immunodeficiency virus</subject><subject>Simian Immunodeficiency Virus - classification</subject><subject>Simian Immunodeficiency Virus - genetics</subject><subject>Simian Immunodeficiency Virus - isolation & purification</subject><subject>Virus 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Evol</addtitle><date>2007-08-01</date><risdate>2007</risdate><volume>24</volume><issue>8</issue><spage>1853</spage><epage>1860</epage><pages>1853-1860</pages><issn>0737-4038</issn><eissn>1537-1719</eissn><abstract>Human 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.</abstract><cop>United States</cop><pub>Oxford University Press</pub><pmid>17545188</pmid><doi>10.1093/molbev/msm110</doi><tpages>8</tpages><oa>free_for_read</oa></addata></record> |
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ispartof | Molecular biology and evolution, 2007-08, Vol.24 (8), p.1853-1860 |
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subjects | Acquired Immunodeficiency Syndrome - epidemiology Acquired Immunodeficiency Syndrome - transmission Acquired Immunodeficiency Syndrome - virology Adaptation Africa, Central Animals Biological Evolution CD4-Positive T-Lymphocytes - metabolism CD4-Positive T-Lymphocytes - virology Evolutionary biology Gene Products, gag - genetics Gene Products, gag - metabolism Genomics HIV HIV-1 - physiology Human immunodeficiency virus Human immunodeficiency virus 1 Humans Lymphocytes Molecular biology Mutagenesis, Site-Directed Mutation - genetics Pan troglodytes Pan troglodytes troglodytes Pandemics Phylogeny Primates Sequence Analysis, DNA Simian Acquired Immunodeficiency Syndrome - epidemiology Simian Acquired Immunodeficiency Syndrome - transmission Simian Acquired Immunodeficiency Syndrome - virology Simian immunodeficiency virus Simian Immunodeficiency Virus - classification Simian Immunodeficiency Virus - genetics Simian Immunodeficiency Virus - isolation & purification Virus Replication |
title | Adaptation of HIV-1 to Its Human Host |
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