Relative rate and location of intra-host HIV evolution to evade cellular immunity are predictable
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Relative rate and location.pdf
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403.91 KB
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Author(s)
Barton, John P
Butler, Thomas Charles
Walker, Bruce
Chakraborty, Arup K
Date Issued
May 2016
Journal
Nature Communications
Publisher
Nature Publishing Group
Citation
Barton, John P. et al. “Relative Rate and Location of Intra-Host HIV Evolution to Evade Cellular Immunity Are Predictable.” Nature Communications 7 (May 2016): 11660
Version
Final published version
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.
MIT Department
Institute for Medical Engineering and Science
Massachusetts Institute of Technology. Department of Biological Engineering
Massachusetts Institute of Technology. Department of Chemical Engineering
Massachusetts Institute of Technology. Department of Chemistry
Massachusetts Institute of Technology. Department of Physics
Terms of Use
Creative Commons Attribution 4.0 International License
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DOI of Published Version
https://doi.org/10.1038/ncomms11660
