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CD8 T cell response and evolutionary pressure to HIV-1 cryptic epitopes derived from antisense transcription
Retroviruses pack multiple genes into relatively small genomes by encoding several genes in the same genomic region with overlapping reading frames. Both sense and antisense HIV-1 transcripts contain open reading frames for known functional proteins as well as numerous alternative reading frames (AR...
Autores principales: | , , , , , , , , , , , , , , , , |
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Formato: | Texto |
Lenguaje: | English |
Publicado: |
The Rockefeller University Press
2010
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2812545/ https://www.ncbi.nlm.nih.gov/pubmed/20065064 http://dx.doi.org/10.1084/jem.20092060 |
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author | Bansal, Anju Carlson, Jonathan Yan, Jiyu Akinsiku, Olusimidele T. Schaefer, Malinda Sabbaj, Steffanie Bet, Anne Levy, David N. Heath, Sonya Tang, Jianming Kaslow, Richard A. Walker, Bruce D. Ndung’u, Thumbi Goulder, Philip J. Heckerman, David Hunter, Eric Goepfert, Paul A. |
author_facet | Bansal, Anju Carlson, Jonathan Yan, Jiyu Akinsiku, Olusimidele T. Schaefer, Malinda Sabbaj, Steffanie Bet, Anne Levy, David N. Heath, Sonya Tang, Jianming Kaslow, Richard A. Walker, Bruce D. Ndung’u, Thumbi Goulder, Philip J. Heckerman, David Hunter, Eric Goepfert, Paul A. |
author_sort | Bansal, Anju |
collection | PubMed |
description | Retroviruses pack multiple genes into relatively small genomes by encoding several genes in the same genomic region with overlapping reading frames. Both sense and antisense HIV-1 transcripts contain open reading frames for known functional proteins as well as numerous alternative reading frames (ARFs). At least some ARFs have the potential to encode proteins of unknown function, and their antigenic properties can be considered as cryptic epitopes (CEs). To examine the extent of active immune response to virally encoded CEs, we analyzed human leukocyte antigen class I–associated polymorphisms in HIV-1 gag, pol, and nef genes from a large cohort of South Africans with chronic infection. In all, 391 CEs and 168 conventional epitopes were predicted, with the majority (307; 79%) of CEs derived from antisense transcripts. In further evaluation of CD8 T cell responses to a subset of the predicted CEs in patients with primary or chronic infection, both sense- and antisense-encoded CEs were immunogenic at both stages of infection. In addition, CEs often mutated during the first year of infection, which was consistent with immune selection for escape variants. These findings indicate that the HIV-1 genome might encode and deploy a large potential repertoire of unconventional epitopes to enhance vaccine-induced antiviral immunity. |
format | Text |
id | pubmed-2812545 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2010 |
publisher | The Rockefeller University Press |
record_format | MEDLINE/PubMed |
spelling | pubmed-28125452010-07-18 CD8 T cell response and evolutionary pressure to HIV-1 cryptic epitopes derived from antisense transcription Bansal, Anju Carlson, Jonathan Yan, Jiyu Akinsiku, Olusimidele T. Schaefer, Malinda Sabbaj, Steffanie Bet, Anne Levy, David N. Heath, Sonya Tang, Jianming Kaslow, Richard A. Walker, Bruce D. Ndung’u, Thumbi Goulder, Philip J. Heckerman, David Hunter, Eric Goepfert, Paul A. J Exp Med Brief Definitive Report Retroviruses pack multiple genes into relatively small genomes by encoding several genes in the same genomic region with overlapping reading frames. Both sense and antisense HIV-1 transcripts contain open reading frames for known functional proteins as well as numerous alternative reading frames (ARFs). At least some ARFs have the potential to encode proteins of unknown function, and their antigenic properties can be considered as cryptic epitopes (CEs). To examine the extent of active immune response to virally encoded CEs, we analyzed human leukocyte antigen class I–associated polymorphisms in HIV-1 gag, pol, and nef genes from a large cohort of South Africans with chronic infection. In all, 391 CEs and 168 conventional epitopes were predicted, with the majority (307; 79%) of CEs derived from antisense transcripts. In further evaluation of CD8 T cell responses to a subset of the predicted CEs in patients with primary or chronic infection, both sense- and antisense-encoded CEs were immunogenic at both stages of infection. In addition, CEs often mutated during the first year of infection, which was consistent with immune selection for escape variants. These findings indicate that the HIV-1 genome might encode and deploy a large potential repertoire of unconventional epitopes to enhance vaccine-induced antiviral immunity. The Rockefeller University Press 2010-01-18 /pmc/articles/PMC2812545/ /pubmed/20065064 http://dx.doi.org/10.1084/jem.20092060 Text en © 2010 Bansal et al. 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.jem.org/misc/terms.shtml). After six months it is available under a Creative Commons License (Attribution–Noncommercial–Share Alike 3.0 Unported license, as described at http://creativecommons.org/licenses/by-nc-sa/3.0/). |
spellingShingle | Brief Definitive Report Bansal, Anju Carlson, Jonathan Yan, Jiyu Akinsiku, Olusimidele T. Schaefer, Malinda Sabbaj, Steffanie Bet, Anne Levy, David N. Heath, Sonya Tang, Jianming Kaslow, Richard A. Walker, Bruce D. Ndung’u, Thumbi Goulder, Philip J. Heckerman, David Hunter, Eric Goepfert, Paul A. CD8 T cell response and evolutionary pressure to HIV-1 cryptic epitopes derived from antisense transcription |
title | CD8 T cell response and evolutionary pressure to HIV-1 cryptic epitopes derived from antisense transcription |
title_full | CD8 T cell response and evolutionary pressure to HIV-1 cryptic epitopes derived from antisense transcription |
title_fullStr | CD8 T cell response and evolutionary pressure to HIV-1 cryptic epitopes derived from antisense transcription |
title_full_unstemmed | CD8 T cell response and evolutionary pressure to HIV-1 cryptic epitopes derived from antisense transcription |
title_short | CD8 T cell response and evolutionary pressure to HIV-1 cryptic epitopes derived from antisense transcription |
title_sort | cd8 t cell response and evolutionary pressure to hiv-1 cryptic epitopes derived from antisense transcription |
topic | Brief Definitive Report |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2812545/ https://www.ncbi.nlm.nih.gov/pubmed/20065064 http://dx.doi.org/10.1084/jem.20092060 |
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