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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.

Original publication

DOI

10.1038/ncomms11660

Type

Journal article

Journal

Nat Commun

Publication Date

23/05/2016

Volume

7

Keywords

Evolution, Molecular, Female, Genetic Fitness, HIV, HIV Infections, Human Immunodeficiency Virus Proteins, Humans, Immunity, Cellular, Male, Models, Genetic, Polyproteins