Genotypic and functional impact of HIV-1 adaptation to its host population during the North American epidemic.
HLA-restricted immune escape mutations that persist following HIV transmission could gradually spread through the viral population, thereby compromising host antiviral immunity as the epidemic progresses. To assess the extent and phenotypic impact of this phenomenon in an immunogenetically diverse p...
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Public Library of Science (PLoS)
2014-04-01
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| Series: | PLoS Genetics |
| Online Access: | https://doi.org/10.1371/journal.pgen.1004295 |
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| author | Laura A Cotton Xiaomei T Kuang Anh Q Le Jonathan M Carlson Benjamin Chan Denis R Chopera Chanson J Brumme Tristan J Markle Eric Martin Aniqa Shahid Gursev Anmole Philip Mwimanzi Pauline Nassab Kali A Penney Manal A Rahman M-J Milloy Martin T Schechter Martin Markowitz Mary Carrington Bruce D Walker Theresa Wagner Susan Buchbinder Jonathan Fuchs Beryl Koblin Kenneth H Mayer P Richard Harrigan Mark A Brockman Art F Y Poon Zabrina L Brumme |
| author_facet | Laura A Cotton Xiaomei T Kuang Anh Q Le Jonathan M Carlson Benjamin Chan Denis R Chopera Chanson J Brumme Tristan J Markle Eric Martin Aniqa Shahid Gursev Anmole Philip Mwimanzi Pauline Nassab Kali A Penney Manal A Rahman M-J Milloy Martin T Schechter Martin Markowitz Mary Carrington Bruce D Walker Theresa Wagner Susan Buchbinder Jonathan Fuchs Beryl Koblin Kenneth H Mayer P Richard Harrigan Mark A Brockman Art F Y Poon Zabrina L Brumme |
| author_sort | Laura A Cotton |
| collection | DOAJ |
| description | HLA-restricted immune escape mutations that persist following HIV transmission could gradually spread through the viral population, thereby compromising host antiviral immunity as the epidemic progresses. To assess the extent and phenotypic impact of this phenomenon in an immunogenetically diverse population, we genotypically and functionally compared linked HLA and HIV (Gag/Nef) sequences from 358 historic (1979-1989) and 382 modern (2000-2011) specimens from four key cities in the North American epidemic (New York, Boston, San Francisco, Vancouver). Inferred HIV phylogenies were star-like, with approximately two-fold greater mean pairwise distances in modern versus historic sequences. The reconstructed epidemic ancestral (founder) HIV sequence was essentially identical to the North American subtype B consensus. Consistent with gradual diversification of a "consensus-like" founder virus, the median "background" frequencies of individual HLA-associated polymorphisms in HIV (in individuals lacking the restricting HLA[s]) were ∼ 2-fold higher in modern versus historic HIV sequences, though these remained notably low overall (e.g. in Gag, medians were 3.7% in the 2000s versus 2.0% in the 1980s). HIV polymorphisms exhibiting the greatest relative spread were those restricted by protective HLAs. Despite these increases, when HIV sequences were analyzed as a whole, their total average burden of polymorphisms that were "pre-adapted" to the average host HLA profile was only ∼ 2% greater in modern versus historic eras. Furthermore, HLA-associated polymorphisms identified in historic HIV sequences were consistent with those detectable today, with none identified that could explain the few HIV codons where the inferred epidemic ancestor differed from the modern consensus. Results are therefore consistent with slow HIV adaptation to HLA, but at a rate unlikely to yield imminent negative implications for cellular immunity, at least in North America. Intriguingly, temporal changes in protein activity of patient-derived Nef (though not Gag) sequences were observed, suggesting functional implications of population-level HIV evolution on certain viral proteins. |
| format | Article |
| id | doaj-art-5120521a2c5e4e9facd0fbd9fe45093e |
| institution | OA Journals |
| issn | 1553-7390 1553-7404 |
| language | English |
| publishDate | 2014-04-01 |
| publisher | Public Library of Science (PLoS) |
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| series | PLoS Genetics |
| spelling | doaj-art-5120521a2c5e4e9facd0fbd9fe45093e2025-08-20T02:22:45ZengPublic Library of Science (PLoS)PLoS Genetics1553-73901553-74042014-04-01104e100429510.1371/journal.pgen.1004295Genotypic and functional impact of HIV-1 adaptation to its host population during the North American epidemic.Laura A CottonXiaomei T KuangAnh Q LeJonathan M CarlsonBenjamin ChanDenis R ChoperaChanson J BrummeTristan J MarkleEric MartinAniqa ShahidGursev AnmolePhilip MwimanziPauline NassabKali A PenneyManal A RahmanM-J MilloyMartin T SchechterMartin MarkowitzMary CarringtonBruce D WalkerTheresa WagnerSusan BuchbinderJonathan FuchsBeryl KoblinKenneth H MayerP Richard HarriganMark A BrockmanArt F Y PoonZabrina L BrummeHLA-restricted immune escape mutations that persist following HIV transmission could gradually spread through the viral population, thereby compromising host antiviral immunity as the epidemic progresses. To assess the extent and phenotypic impact of this phenomenon in an immunogenetically diverse population, we genotypically and functionally compared linked HLA and HIV (Gag/Nef) sequences from 358 historic (1979-1989) and 382 modern (2000-2011) specimens from four key cities in the North American epidemic (New York, Boston, San Francisco, Vancouver). Inferred HIV phylogenies were star-like, with approximately two-fold greater mean pairwise distances in modern versus historic sequences. The reconstructed epidemic ancestral (founder) HIV sequence was essentially identical to the North American subtype B consensus. Consistent with gradual diversification of a "consensus-like" founder virus, the median "background" frequencies of individual HLA-associated polymorphisms in HIV (in individuals lacking the restricting HLA[s]) were ∼ 2-fold higher in modern versus historic HIV sequences, though these remained notably low overall (e.g. in Gag, medians were 3.7% in the 2000s versus 2.0% in the 1980s). HIV polymorphisms exhibiting the greatest relative spread were those restricted by protective HLAs. Despite these increases, when HIV sequences were analyzed as a whole, their total average burden of polymorphisms that were "pre-adapted" to the average host HLA profile was only ∼ 2% greater in modern versus historic eras. Furthermore, HLA-associated polymorphisms identified in historic HIV sequences were consistent with those detectable today, with none identified that could explain the few HIV codons where the inferred epidemic ancestor differed from the modern consensus. Results are therefore consistent with slow HIV adaptation to HLA, but at a rate unlikely to yield imminent negative implications for cellular immunity, at least in North America. Intriguingly, temporal changes in protein activity of patient-derived Nef (though not Gag) sequences were observed, suggesting functional implications of population-level HIV evolution on certain viral proteins.https://doi.org/10.1371/journal.pgen.1004295 |
| spellingShingle | Laura A Cotton Xiaomei T Kuang Anh Q Le Jonathan M Carlson Benjamin Chan Denis R Chopera Chanson J Brumme Tristan J Markle Eric Martin Aniqa Shahid Gursev Anmole Philip Mwimanzi Pauline Nassab Kali A Penney Manal A Rahman M-J Milloy Martin T Schechter Martin Markowitz Mary Carrington Bruce D Walker Theresa Wagner Susan Buchbinder Jonathan Fuchs Beryl Koblin Kenneth H Mayer P Richard Harrigan Mark A Brockman Art F Y Poon Zabrina L Brumme Genotypic and functional impact of HIV-1 adaptation to its host population during the North American epidemic. PLoS Genetics |
| title | Genotypic and functional impact of HIV-1 adaptation to its host population during the North American epidemic. |
| title_full | Genotypic and functional impact of HIV-1 adaptation to its host population during the North American epidemic. |
| title_fullStr | Genotypic and functional impact of HIV-1 adaptation to its host population during the North American epidemic. |
| title_full_unstemmed | Genotypic and functional impact of HIV-1 adaptation to its host population during the North American epidemic. |
| title_short | Genotypic and functional impact of HIV-1 adaptation to its host population during the North American epidemic. |
| title_sort | genotypic and functional impact of hiv 1 adaptation to its host population during the north american epidemic |
| url | https://doi.org/10.1371/journal.pgen.1004295 |
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