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

John P. Barton, Nilu Goonetilleke, Thomas C. Butler, Bruce D. Walker, Andrew J. McMichael, Arup K. Chakraborty

Research output: Contribution to journalArticlepeer-review

74 Scopus citations

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.

Original languageEnglish
Article number11660
JournalNature Communications
Volume7
DOIs
StatePublished - 23 May 2016
Externally publishedYes

Bibliographical note

Funding Information:
This research was funded by the Ragon Institute of MGH, MIT and Harvard (J.P.B., A.K.C. and B.D.W.), National Institute of Allergy and Infectious Diseases, Center for HIV/AIDS Vaccine Immunology and Immunogen Discovery Grant UM1-AI100663 (to B.D.W.), a Creative and Novel Ideas in HIV Research award P30 AI9227763 (to N.G.) and the Center for HIV/AIDS Vaccine Immunology and Immunogen Discovery Grant UM1-AI100645-01 (to A.J.M.).

Funding

This research was funded by the Ragon Institute of MGH, MIT and Harvard (J.P.B., A.K.C. and B.D.W.), National Institute of Allergy and Infectious Diseases, Center for HIV/AIDS Vaccine Immunology and Immunogen Discovery Grant UM1-AI100663 (to B.D.W.), a Creative and Novel Ideas in HIV Research award P30 AI9227763 (to N.G.) and the Center for HIV/AIDS Vaccine Immunology and Immunogen Discovery Grant UM1-AI100645-01 (to A.J.M.).

FundersFunder number
Ragon Institute of MGH
National Institute of Allergy and Infectious DiseasesP30 AI9227763, UM1-AI100663, UM1AI100645
Massachusetts Institute of Technology
Harvard University
Medical Research CouncilMR/K012037/1

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