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Role of HIV-specific CD8(+) T cells in pediatric HIV cure strategies after widespread early viral escape
Recent studies have suggested greater HIV cure potential among infected children than adults. A major obstacle to HIV eradication in adults is that the viral reservoir is largely comprised of HIV-specific cytotoxic T lymphocyte (CTL) escape variants. We here evaluate the potential for CTL in HIV-inf...
Autores principales: | , , , , , , , , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
The Rockefeller University Press
2017
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5679167/ https://www.ncbi.nlm.nih.gov/pubmed/28983013 http://dx.doi.org/10.1084/jem.20162123 |
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author | Leitman, Ellen M. Thobakgale, Christina F. Adland, Emily Ansari, M. Azim Raghwani, Jayna Prendergast, Andrew J. Tudor-Williams, Gareth Kiepiela, Photini Hemelaar, Joris Brener, Jacqui Tsai, Ming-Han Mori, Masahiko Riddell, Lynn Luzzi, Graz Jooste, Pieter Ndung’u, Thumbi Walker, Bruce D. Pybus, Oliver G. Kellam, Paul Naranbhai, Vivek Matthews, Philippa C. Gall, Astrid Goulder, Philip J.R. |
author_facet | Leitman, Ellen M. Thobakgale, Christina F. Adland, Emily Ansari, M. Azim Raghwani, Jayna Prendergast, Andrew J. Tudor-Williams, Gareth Kiepiela, Photini Hemelaar, Joris Brener, Jacqui Tsai, Ming-Han Mori, Masahiko Riddell, Lynn Luzzi, Graz Jooste, Pieter Ndung’u, Thumbi Walker, Bruce D. Pybus, Oliver G. Kellam, Paul Naranbhai, Vivek Matthews, Philippa C. Gall, Astrid Goulder, Philip J.R. |
author_sort | Leitman, Ellen M. |
collection | PubMed |
description | Recent studies have suggested greater HIV cure potential among infected children than adults. A major obstacle to HIV eradication in adults is that the viral reservoir is largely comprised of HIV-specific cytotoxic T lymphocyte (CTL) escape variants. We here evaluate the potential for CTL in HIV-infected slow-progressor children to play an effective role in “shock-and-kill” cure strategies. Two distinct subgroups of children were identified on the basis of viral load. Unexpectedly, in both groups, as in adults, HIV-specific CTL drove the selection of escape variants across a range of epitopes within the first weeks of infection. However, in HIV-infected children, but not adults, de novo autologous variant-specific CTL responses were generated, enabling the pediatric immune system to “corner” the virus. Thus, even when escape variants are selected in early infection, the capacity in children to generate variant-specific anti-HIV CTL responses maintains the potential for CTL to contribute to effective shock-and-kill cure strategies in pediatric HIV infection. |
format | Online Article Text |
id | pubmed-5679167 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2017 |
publisher | The Rockefeller University Press |
record_format | MEDLINE/PubMed |
spelling | pubmed-56791672018-05-06 Role of HIV-specific CD8(+) T cells in pediatric HIV cure strategies after widespread early viral escape Leitman, Ellen M. Thobakgale, Christina F. Adland, Emily Ansari, M. Azim Raghwani, Jayna Prendergast, Andrew J. Tudor-Williams, Gareth Kiepiela, Photini Hemelaar, Joris Brener, Jacqui Tsai, Ming-Han Mori, Masahiko Riddell, Lynn Luzzi, Graz Jooste, Pieter Ndung’u, Thumbi Walker, Bruce D. Pybus, Oliver G. Kellam, Paul Naranbhai, Vivek Matthews, Philippa C. Gall, Astrid Goulder, Philip J.R. J Exp Med Research Articles Recent studies have suggested greater HIV cure potential among infected children than adults. A major obstacle to HIV eradication in adults is that the viral reservoir is largely comprised of HIV-specific cytotoxic T lymphocyte (CTL) escape variants. We here evaluate the potential for CTL in HIV-infected slow-progressor children to play an effective role in “shock-and-kill” cure strategies. Two distinct subgroups of children were identified on the basis of viral load. Unexpectedly, in both groups, as in adults, HIV-specific CTL drove the selection of escape variants across a range of epitopes within the first weeks of infection. However, in HIV-infected children, but not adults, de novo autologous variant-specific CTL responses were generated, enabling the pediatric immune system to “corner” the virus. Thus, even when escape variants are selected in early infection, the capacity in children to generate variant-specific anti-HIV CTL responses maintains the potential for CTL to contribute to effective shock-and-kill cure strategies in pediatric HIV infection. The Rockefeller University Press 2017-11-06 /pmc/articles/PMC5679167/ /pubmed/28983013 http://dx.doi.org/10.1084/jem.20162123 Text en © 2017 Leitman et al. http://www.rupress.org/terms/https://creativecommons.org/licenses/by-nc-sa/4.0/This article is distributed under the terms of an Attribution–Noncommercial–Share Alike–No Mirror Sites license for the first six months after the publication date (see http://www.rupress.org/terms/). After six months it is available under a Creative Commons License (Attribution–Noncommercial–Share Alike 4.0 International license, as described at https://creativecommons.org/licenses/by-nc-sa/4.0/). |
spellingShingle | Research Articles Leitman, Ellen M. Thobakgale, Christina F. Adland, Emily Ansari, M. Azim Raghwani, Jayna Prendergast, Andrew J. Tudor-Williams, Gareth Kiepiela, Photini Hemelaar, Joris Brener, Jacqui Tsai, Ming-Han Mori, Masahiko Riddell, Lynn Luzzi, Graz Jooste, Pieter Ndung’u, Thumbi Walker, Bruce D. Pybus, Oliver G. Kellam, Paul Naranbhai, Vivek Matthews, Philippa C. Gall, Astrid Goulder, Philip J.R. Role of HIV-specific CD8(+) T cells in pediatric HIV cure strategies after widespread early viral escape |
title | Role of HIV-specific CD8(+) T cells in pediatric HIV cure strategies after widespread early viral escape |
title_full | Role of HIV-specific CD8(+) T cells in pediatric HIV cure strategies after widespread early viral escape |
title_fullStr | Role of HIV-specific CD8(+) T cells in pediatric HIV cure strategies after widespread early viral escape |
title_full_unstemmed | Role of HIV-specific CD8(+) T cells in pediatric HIV cure strategies after widespread early viral escape |
title_short | Role of HIV-specific CD8(+) T cells in pediatric HIV cure strategies after widespread early viral escape |
title_sort | role of hiv-specific cd8(+) t cells in pediatric hiv cure strategies after widespread early viral escape |
topic | Research Articles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5679167/ https://www.ncbi.nlm.nih.gov/pubmed/28983013 http://dx.doi.org/10.1084/jem.20162123 |
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