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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Veröffentlicht in:Molecular biology and evolution 2007-08, Vol.24 (8), p.1853-1860
Hauptverfasser: 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.
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container_end_page 1860
container_issue 8
container_start_page 1853
container_title Molecular biology and evolution
container_volume 24
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. 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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. 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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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