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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...

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Autores principales: 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.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: The Rockefeller University Press 2017
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.
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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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