|Title||Relative rate and location of intra-host HIV evolution to evade cellular immunity are predictable.|
|Publication Type||Journal Article|
|Year of Publication||2016|
|Authors||Barton JP, Goonetilleke N, Butler TC, Walker BD, McMichael AJ, Chakraborty AK|
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.
|Alternate Journal||Nat Commun|
|PubMed Central ID||PMC4879252|
|Grant List||UM1 AI100645 / AI / NIAID NIH HHS / United States |
UM1 AI100663 / AI / NIAID NIH HHS / United States
Relative rate and location of intra-host HIV evolution to evade cellular immunity are predictable.