Cargando…

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...

Descripción completa

Detalles Bibliográficos
Autores principales: 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.
Formato: Texto
Lenguaje:English
Publicado: The Rockefeller University Press 2010
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
_version_ 1782176844261359616
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
work_keys_str_mv AT bansalanju cd8tcellresponseandevolutionarypressuretohiv1crypticepitopesderivedfromantisensetranscription
AT carlsonjonathan cd8tcellresponseandevolutionarypressuretohiv1crypticepitopesderivedfromantisensetranscription
AT yanjiyu cd8tcellresponseandevolutionarypressuretohiv1crypticepitopesderivedfromantisensetranscription
AT akinsikuolusimidelet cd8tcellresponseandevolutionarypressuretohiv1crypticepitopesderivedfromantisensetranscription
AT schaefermalinda cd8tcellresponseandevolutionarypressuretohiv1crypticepitopesderivedfromantisensetranscription
AT sabbajsteffanie cd8tcellresponseandevolutionarypressuretohiv1crypticepitopesderivedfromantisensetranscription
AT betanne cd8tcellresponseandevolutionarypressuretohiv1crypticepitopesderivedfromantisensetranscription
AT levydavidn cd8tcellresponseandevolutionarypressuretohiv1crypticepitopesderivedfromantisensetranscription
AT heathsonya cd8tcellresponseandevolutionarypressuretohiv1crypticepitopesderivedfromantisensetranscription
AT tangjianming cd8tcellresponseandevolutionarypressuretohiv1crypticepitopesderivedfromantisensetranscription
AT kaslowricharda cd8tcellresponseandevolutionarypressuretohiv1crypticepitopesderivedfromantisensetranscription
AT walkerbruced cd8tcellresponseandevolutionarypressuretohiv1crypticepitopesderivedfromantisensetranscription
AT ndunguthumbi cd8tcellresponseandevolutionarypressuretohiv1crypticepitopesderivedfromantisensetranscription
AT goulderphilipj cd8tcellresponseandevolutionarypressuretohiv1crypticepitopesderivedfromantisensetranscription
AT heckermandavid cd8tcellresponseandevolutionarypressuretohiv1crypticepitopesderivedfromantisensetranscription
AT huntereric cd8tcellresponseandevolutionarypressuretohiv1crypticepitopesderivedfromantisensetranscription
AT goepfertpaula cd8tcellresponseandevolutionarypressuretohiv1crypticepitopesderivedfromantisensetranscription