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Relative rate and location of intra-host HIV evolution to evade cellular immunity are predictable
Human immunodeficiency virus (HIV) evolves within infected persons to escape being destroyed by the host immune system, thereby preventing effective immune control of infection. Here, we combine methods from evolutionary dynamics and statistical physics to simulate in vivo HIV sequence evolution, pr...
Autores principales: | , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group
2016
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4879252/ https://www.ncbi.nlm.nih.gov/pubmed/27212475 http://dx.doi.org/10.1038/ncomms11660 |
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author | Barton, John P. Goonetilleke, Nilu Butler, Thomas C. Walker, Bruce D. McMichael, Andrew J. Chakraborty, Arup K. |
author_facet | Barton, John P. Goonetilleke, Nilu Butler, Thomas C. Walker, Bruce D. McMichael, Andrew J. Chakraborty, Arup K. |
author_sort | Barton, John P. |
collection | PubMed |
description | Human immunodeficiency virus (HIV) evolves within infected persons to escape being destroyed by the host immune system, thereby preventing effective immune control of infection. Here, we combine methods from evolutionary dynamics and statistical physics to simulate in vivo HIV sequence evolution, predicting the relative rate of escape and the location of escape mutations in response to T-cell-mediated immune pressure in a cohort of 17 persons with acute HIV infection. Predicted and clinically observed times to escape immune responses agree well, and we show that the mutational pathways to escape depend on the viral sequence background due to epistatic interactions. The ability to predict escape pathways and the duration over which control is maintained by specific immune responses open the door to rational design of immunotherapeutic strategies that might enable long-term control of HIV infection. Our approach enables intra-host evolution of a human pathogen to be predicted in a probabilistic framework. |
format | Online Article Text |
id | pubmed-4879252 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2016 |
publisher | Nature Publishing Group |
record_format | MEDLINE/PubMed |
spelling | pubmed-48792522016-06-02 Relative rate and location of intra-host HIV evolution to evade cellular immunity are predictable Barton, John P. Goonetilleke, Nilu Butler, Thomas C. Walker, Bruce D. McMichael, Andrew J. Chakraborty, Arup K. Nat Commun Article Human immunodeficiency virus (HIV) evolves within infected persons to escape being destroyed by the host immune system, thereby preventing effective immune control of infection. Here, we combine methods from evolutionary dynamics and statistical physics to simulate in vivo HIV sequence evolution, predicting the relative rate of escape and the location of escape mutations in response to T-cell-mediated immune pressure in a cohort of 17 persons with acute HIV infection. Predicted and clinically observed times to escape immune responses agree well, and we show that the mutational pathways to escape depend on the viral sequence background due to epistatic interactions. The ability to predict escape pathways and the duration over which control is maintained by specific immune responses open the door to rational design of immunotherapeutic strategies that might enable long-term control of HIV infection. Our approach enables intra-host evolution of a human pathogen to be predicted in a probabilistic framework. Nature Publishing Group 2016-05-23 /pmc/articles/PMC4879252/ /pubmed/27212475 http://dx.doi.org/10.1038/ncomms11660 Text en Copyright © 2016, Nature Publishing Group, a division of Macmillan Publishers Limited. All Rights Reserved. http://creativecommons.org/licenses/by/4.0/ This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article's Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/ |
spellingShingle | Article Barton, John P. Goonetilleke, Nilu Butler, Thomas C. Walker, Bruce D. McMichael, Andrew J. Chakraborty, Arup K. Relative rate and location of intra-host HIV evolution to evade cellular immunity are predictable |
title | Relative rate and location of intra-host HIV evolution to evade cellular immunity are predictable |
title_full | Relative rate and location of intra-host HIV evolution to evade cellular immunity are predictable |
title_fullStr | Relative rate and location of intra-host HIV evolution to evade cellular immunity are predictable |
title_full_unstemmed | Relative rate and location of intra-host HIV evolution to evade cellular immunity are predictable |
title_short | Relative rate and location of intra-host HIV evolution to evade cellular immunity are predictable |
title_sort | relative rate and location of intra-host hiv evolution to evade cellular immunity are predictable |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4879252/ https://www.ncbi.nlm.nih.gov/pubmed/27212475 http://dx.doi.org/10.1038/ncomms11660 |
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