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Dynamics of Viral Evolution and CTL Responses in HIV-1 Infection
Improved understanding of the dynamics of host immune responses and viral evolution is critical for effective HIV-1 vaccine design. We comprehensively analyzed Cytotoxic T-lymphocyte (CTL)-viral epitope dynamics in an antiretroviral therapy-naïve subject over the first four years of HIV-1 infection....
Autores principales: | , , , , |
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Formato: | Texto |
Lenguaje: | English |
Publicado: |
Public Library of Science
2011
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3024315/ https://www.ncbi.nlm.nih.gov/pubmed/21283794 http://dx.doi.org/10.1371/journal.pone.0015639 |
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author | Liu, Yi McNevin, John P. Holte, Sarah McElrath, M. Juliana Mullins, James I. |
author_facet | Liu, Yi McNevin, John P. Holte, Sarah McElrath, M. Juliana Mullins, James I. |
author_sort | Liu, Yi |
collection | PubMed |
description | Improved understanding of the dynamics of host immune responses and viral evolution is critical for effective HIV-1 vaccine design. We comprehensively analyzed Cytotoxic T-lymphocyte (CTL)-viral epitope dynamics in an antiretroviral therapy-naïve subject over the first four years of HIV-1 infection. We found that CTL responses developed sequentially and required constant antigenic stimulation for maintenance. CTL responses exerting strong selective pressure emerged early and led to rapid escape, proliferated rapidly and were predominant during acute/early infection. Although CTL responses to a few persistent epitopes developed over the first two months of infection, they proliferated slowly. As CTL epitopes were replaced by mutational variants, the corresponding responses immediately declined, most rapidly in the cases of strongly selected epitopes. CTL recognition of epitope variants, via cross-reactivity and de novo responses, was common throughout the period of study. Our data demonstrate that HIV-specific CTL responses, especially in the critical acute/early stage, were focused on regions that are prone to escape. Failure of CTL responses to strongly target functional or structurally critical regions of the virus, as well as the sequential cascade of CTL responses, followed closely by viral escape and decline of the corresponding responses, likely contribute to a lack of sustainable viral suppression. Focusing early and rapidly proliferating CTL on persistent epitopes may be essential for durable viral control in HIV-1 infection. |
format | Text |
id | pubmed-3024315 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2011 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-30243152011-01-31 Dynamics of Viral Evolution and CTL Responses in HIV-1 Infection Liu, Yi McNevin, John P. Holte, Sarah McElrath, M. Juliana Mullins, James I. PLoS One Research Article Improved understanding of the dynamics of host immune responses and viral evolution is critical for effective HIV-1 vaccine design. We comprehensively analyzed Cytotoxic T-lymphocyte (CTL)-viral epitope dynamics in an antiretroviral therapy-naïve subject over the first four years of HIV-1 infection. We found that CTL responses developed sequentially and required constant antigenic stimulation for maintenance. CTL responses exerting strong selective pressure emerged early and led to rapid escape, proliferated rapidly and were predominant during acute/early infection. Although CTL responses to a few persistent epitopes developed over the first two months of infection, they proliferated slowly. As CTL epitopes were replaced by mutational variants, the corresponding responses immediately declined, most rapidly in the cases of strongly selected epitopes. CTL recognition of epitope variants, via cross-reactivity and de novo responses, was common throughout the period of study. Our data demonstrate that HIV-specific CTL responses, especially in the critical acute/early stage, were focused on regions that are prone to escape. Failure of CTL responses to strongly target functional or structurally critical regions of the virus, as well as the sequential cascade of CTL responses, followed closely by viral escape and decline of the corresponding responses, likely contribute to a lack of sustainable viral suppression. Focusing early and rapidly proliferating CTL on persistent epitopes may be essential for durable viral control in HIV-1 infection. Public Library of Science 2011-01-20 /pmc/articles/PMC3024315/ /pubmed/21283794 http://dx.doi.org/10.1371/journal.pone.0015639 Text en Liu et al. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited. |
spellingShingle | Research Article Liu, Yi McNevin, John P. Holte, Sarah McElrath, M. Juliana Mullins, James I. Dynamics of Viral Evolution and CTL Responses in HIV-1 Infection |
title | Dynamics of Viral Evolution and CTL Responses in HIV-1 Infection |
title_full | Dynamics of Viral Evolution and CTL Responses in HIV-1 Infection |
title_fullStr | Dynamics of Viral Evolution and CTL Responses in HIV-1 Infection |
title_full_unstemmed | Dynamics of Viral Evolution and CTL Responses in HIV-1 Infection |
title_short | Dynamics of Viral Evolution and CTL Responses in HIV-1 Infection |
title_sort | dynamics of viral evolution and ctl responses in hiv-1 infection |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3024315/ https://www.ncbi.nlm.nih.gov/pubmed/21283794 http://dx.doi.org/10.1371/journal.pone.0015639 |
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