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Evasion of adaptive immunity by HIV through the action of host APOBEC3G/F enzymes
APOBEC3G (A3G) and APOBEC3F (A3F) are DNA-mutating enzymes expressed in T cells, dendritic cells and macrophages. A3G/F have been considered innate immune host factors, based on reports that they lethally mutate the HIV genome in vitro. In vivo, A3G/F effectiveness is limited by viral proteins, entr...
Autores principales: | , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
BioMed Central
2017
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5594601/ https://www.ncbi.nlm.nih.gov/pubmed/28893290 http://dx.doi.org/10.1186/s12981-017-0173-8 |
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author | Grant, Michael Larijani, Mani |
author_facet | Grant, Michael Larijani, Mani |
author_sort | Grant, Michael |
collection | PubMed |
description | APOBEC3G (A3G) and APOBEC3F (A3F) are DNA-mutating enzymes expressed in T cells, dendritic cells and macrophages. A3G/F have been considered innate immune host factors, based on reports that they lethally mutate the HIV genome in vitro. In vivo, A3G/F effectiveness is limited by viral proteins, entrapment in inactive complexes and filtration of mutations during viral life cycle. We hypothesized that the impact of sub-lethal A3G/F action could extend beyond the realm of innate immunity confined to the cytoplasm of infected cells. We measured recognition of wild type and A3G/F-mutated epitopes by cytotoxic T lymphocytes (CTL) from HIV-infected individuals and found that A3G/F-induced mutations overwhelmingly diminished CTL recognition of HIV peptides, in a human histocompatibility-linked leukocyte antigen (HLA)-dependent manner. Furthermore, we found corresponding enrichment of A3G/F-favored motifs in CTL epitope-encoding sequences within the HIV genome. These findings illustrate that A3G/F‐mediated mutations mediate immune evasion by HIV in vivo. Therefore, we suggest that vaccine strategies target T cell or antibody epitopes that are not poised for mutation into escape variants by A3G/F action. |
format | Online Article Text |
id | pubmed-5594601 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2017 |
publisher | BioMed Central |
record_format | MEDLINE/PubMed |
spelling | pubmed-55946012017-09-15 Evasion of adaptive immunity by HIV through the action of host APOBEC3G/F enzymes Grant, Michael Larijani, Mani AIDS Res Ther Review APOBEC3G (A3G) and APOBEC3F (A3F) are DNA-mutating enzymes expressed in T cells, dendritic cells and macrophages. A3G/F have been considered innate immune host factors, based on reports that they lethally mutate the HIV genome in vitro. In vivo, A3G/F effectiveness is limited by viral proteins, entrapment in inactive complexes and filtration of mutations during viral life cycle. We hypothesized that the impact of sub-lethal A3G/F action could extend beyond the realm of innate immunity confined to the cytoplasm of infected cells. We measured recognition of wild type and A3G/F-mutated epitopes by cytotoxic T lymphocytes (CTL) from HIV-infected individuals and found that A3G/F-induced mutations overwhelmingly diminished CTL recognition of HIV peptides, in a human histocompatibility-linked leukocyte antigen (HLA)-dependent manner. Furthermore, we found corresponding enrichment of A3G/F-favored motifs in CTL epitope-encoding sequences within the HIV genome. These findings illustrate that A3G/F‐mediated mutations mediate immune evasion by HIV in vivo. Therefore, we suggest that vaccine strategies target T cell or antibody epitopes that are not poised for mutation into escape variants by A3G/F action. BioMed Central 2017-09-12 /pmc/articles/PMC5594601/ /pubmed/28893290 http://dx.doi.org/10.1186/s12981-017-0173-8 Text en © The Author(s) 2017 Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated. |
spellingShingle | Review Grant, Michael Larijani, Mani Evasion of adaptive immunity by HIV through the action of host APOBEC3G/F enzymes |
title | Evasion of adaptive immunity by HIV through the action of host APOBEC3G/F enzymes |
title_full | Evasion of adaptive immunity by HIV through the action of host APOBEC3G/F enzymes |
title_fullStr | Evasion of adaptive immunity by HIV through the action of host APOBEC3G/F enzymes |
title_full_unstemmed | Evasion of adaptive immunity by HIV through the action of host APOBEC3G/F enzymes |
title_short | Evasion of adaptive immunity by HIV through the action of host APOBEC3G/F enzymes |
title_sort | evasion of adaptive immunity by hiv through the action of host apobec3g/f enzymes |
topic | Review |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5594601/ https://www.ncbi.nlm.nih.gov/pubmed/28893290 http://dx.doi.org/10.1186/s12981-017-0173-8 |
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