Relative rate and location of intra-host HIV evolution to evade cellular immunity are predictable.

TitleRelative rate and location of intra-host HIV evolution to evade cellular immunity are predictable.
Publication TypeJournal Article
Year of Publication2016
AuthorsBarton JP, Goonetilleke N, Butler TC, Walker BD, McMichael AJ, Chakraborty AK
JournalNat Commun
Volume7
Pagination11660
Date Published05/23/2016
ISSN2041-1723
Abstract

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.

DOI10.1038/ncomms11660
Alternate JournalNat Commun
PubMed ID27212475
PubMed Central IDPMC4879252
Grant ListUM1 AI100645 / AI / NIAID NIH HHS / United States
UM1 AI100663 / AI / NIAID NIH HHS / United States
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