Transmitted virus fitness and host T cell responses collectively define divergent infection outcomes in two HIV-1 recipients.
Control of virus replication in HIV-1 infection is critical to delaying disease progression. While cellular immune responses are a key determinant of control, relatively little is known about the contribution of the infecting virus to this process. To gain insight into this interplay between virus a...
| Main Authors: | , , , , , , , , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Public Library of Science (PLoS)
2015-01-01
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| Series: | PLoS Pathogens |
| Online Access: | https://doi.org/10.1371/journal.ppat.1004565 |
| _version_ | 1818582038124429312 |
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| author | Ling Yue Katja J Pfafferott Joshua Baalwa Karen Conrod Catherine C Dong Cecilia Chui Rong Rong Daniel T Claiborne Jessica L Prince Jianming Tang Ruy M Ribeiro Emmanuel Cormier Beatrice H Hahn Alan S Perelson George M Shaw Etienne Karita Jill Gilmour Paul Goepfert Cynthia A Derdeyn Susan A Allen Persephone Borrow Eric Hunter |
| author_facet | Ling Yue Katja J Pfafferott Joshua Baalwa Karen Conrod Catherine C Dong Cecilia Chui Rong Rong Daniel T Claiborne Jessica L Prince Jianming Tang Ruy M Ribeiro Emmanuel Cormier Beatrice H Hahn Alan S Perelson George M Shaw Etienne Karita Jill Gilmour Paul Goepfert Cynthia A Derdeyn Susan A Allen Persephone Borrow Eric Hunter |
| author_sort | Ling Yue |
| collection | DOAJ |
| description | Control of virus replication in HIV-1 infection is critical to delaying disease progression. While cellular immune responses are a key determinant of control, relatively little is known about the contribution of the infecting virus to this process. To gain insight into this interplay between virus and host in viral control, we conducted a detailed analysis of two heterosexual HIV-1 subtype A transmission pairs in which female recipients sharing three HLA class I alleles exhibited contrasting clinical outcomes: R880F controlled virus replication while R463F experienced high viral loads and rapid disease progression. Near full-length single genome amplification defined the infecting transmitted/founder (T/F) virus proteome and subsequent sequence evolution over the first year of infection for both acutely infected recipients. T/F virus replicative capacities were compared in vitro, while the development of the earliest cellular immune response was defined using autologous virus sequence-based peptides. The R880F T/F virus replicated significantly slower in vitro than that transmitted to R463F. While neutralizing antibody responses were similar in both subjects, during acute infection R880F mounted a broad T cell response, the most dominant components of which targeted epitopes from which escape was limited. In contrast, the primary HIV-specific T cell response in R463F was focused on just two epitopes, one of which rapidly escaped. This comprehensive study highlights both the importance of the contribution of the lower replication capacity of the transmitted/founder virus and an associated induction of a broad primary HIV-specific T cell response, which was not undermined by rapid epitope escape, to long-term viral control in HIV-1 infection. It underscores the importance of the earliest CD8 T cell response targeting regions of the virus proteome that cannot mutate without a high fitness cost, further emphasizing the need for vaccines that elicit a breadth of T cell responses to conserved viral epitopes. |
| first_indexed | 2024-12-16T07:43:02Z |
| format | Article |
| id | doaj.art-62cfd68ece434b5d8d042bf65beeb14b |
| institution | Directory Open Access Journal |
| issn | 1553-7366 1553-7374 |
| language | English |
| last_indexed | 2024-12-16T07:43:02Z |
| publishDate | 2015-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS Pathogens |
| spelling | doaj.art-62cfd68ece434b5d8d042bf65beeb14b2022-12-21T22:39:03ZengPublic Library of Science (PLoS)PLoS Pathogens1553-73661553-73742015-01-01111e100456510.1371/journal.ppat.1004565Transmitted virus fitness and host T cell responses collectively define divergent infection outcomes in two HIV-1 recipients.Ling YueKatja J PfafferottJoshua BaalwaKaren ConrodCatherine C DongCecilia ChuiRong RongDaniel T ClaiborneJessica L PrinceJianming TangRuy M RibeiroEmmanuel CormierBeatrice H HahnAlan S PerelsonGeorge M ShawEtienne KaritaJill GilmourPaul GoepfertCynthia A DerdeynSusan A AllenPersephone BorrowEric HunterControl of virus replication in HIV-1 infection is critical to delaying disease progression. While cellular immune responses are a key determinant of control, relatively little is known about the contribution of the infecting virus to this process. To gain insight into this interplay between virus and host in viral control, we conducted a detailed analysis of two heterosexual HIV-1 subtype A transmission pairs in which female recipients sharing three HLA class I alleles exhibited contrasting clinical outcomes: R880F controlled virus replication while R463F experienced high viral loads and rapid disease progression. Near full-length single genome amplification defined the infecting transmitted/founder (T/F) virus proteome and subsequent sequence evolution over the first year of infection for both acutely infected recipients. T/F virus replicative capacities were compared in vitro, while the development of the earliest cellular immune response was defined using autologous virus sequence-based peptides. The R880F T/F virus replicated significantly slower in vitro than that transmitted to R463F. While neutralizing antibody responses were similar in both subjects, during acute infection R880F mounted a broad T cell response, the most dominant components of which targeted epitopes from which escape was limited. In contrast, the primary HIV-specific T cell response in R463F was focused on just two epitopes, one of which rapidly escaped. This comprehensive study highlights both the importance of the contribution of the lower replication capacity of the transmitted/founder virus and an associated induction of a broad primary HIV-specific T cell response, which was not undermined by rapid epitope escape, to long-term viral control in HIV-1 infection. It underscores the importance of the earliest CD8 T cell response targeting regions of the virus proteome that cannot mutate without a high fitness cost, further emphasizing the need for vaccines that elicit a breadth of T cell responses to conserved viral epitopes.https://doi.org/10.1371/journal.ppat.1004565 |
| spellingShingle | Ling Yue Katja J Pfafferott Joshua Baalwa Karen Conrod Catherine C Dong Cecilia Chui Rong Rong Daniel T Claiborne Jessica L Prince Jianming Tang Ruy M Ribeiro Emmanuel Cormier Beatrice H Hahn Alan S Perelson George M Shaw Etienne Karita Jill Gilmour Paul Goepfert Cynthia A Derdeyn Susan A Allen Persephone Borrow Eric Hunter Transmitted virus fitness and host T cell responses collectively define divergent infection outcomes in two HIV-1 recipients. PLoS Pathogens |
| title | Transmitted virus fitness and host T cell responses collectively define divergent infection outcomes in two HIV-1 recipients. |
| title_full | Transmitted virus fitness and host T cell responses collectively define divergent infection outcomes in two HIV-1 recipients. |
| title_fullStr | Transmitted virus fitness and host T cell responses collectively define divergent infection outcomes in two HIV-1 recipients. |
| title_full_unstemmed | Transmitted virus fitness and host T cell responses collectively define divergent infection outcomes in two HIV-1 recipients. |
| title_short | Transmitted virus fitness and host T cell responses collectively define divergent infection outcomes in two HIV-1 recipients. |
| title_sort | transmitted virus fitness and host t cell responses collectively define divergent infection outcomes in two hiv 1 recipients |
| url | https://doi.org/10.1371/journal.ppat.1004565 |
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