title: Relative rate and location of intra-host HIV evolution to evade cellular immunity are predictable.
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.
authors.affiliation: Ragon Institute of MGH, MIT and Harvard, Cambridge, Massachusetts 02139, USA.|Department of Chemical Engineering, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, USA.|Department of Physics, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, USA.|Institute for Medical Engineering and Science, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, USA.
authors.forename: John P
authors.identifier: http://orcid.org/0000-0003-1467-421X
authors.initials: JP
authors.lastname: Barton
authors.affiliation: Department of Microbiology, Immunology and Medicine, University of North Carolina, Chapel Hill, North Carolina 27599, USA.|Nuffield Department of Medicine, University of Oxford, Old Road Campus, Headington, Oxford OX3 7FZ, UK.
authors.forename: Nilu
authors.initials: N
authors.lastname: Goonetilleke
authors.affiliation: Department of Chemical Engineering, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, USA.|Department of Physics, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, USA.
authors.forename: Thomas C
authors.initials: TC
authors.lastname: Butler
authors.affiliation: Ragon Institute of MGH, MIT and Harvard, Cambridge, Massachusetts 02139, USA.|Howard Hughes Medical Institute, Chevy Chase, Maryland 20815, USA.
authors.forename: Bruce D
authors.initials: BD
authors.lastname: Walker
authors.affiliation: Nuffield Department of Medicine, University of Oxford, Old Road Campus, Headington, Oxford OX3 7FZ, UK.
authors.forename: Andrew J
authors.initials: AJ
authors.lastname: McMichael
authors.affiliation: Ragon Institute of MGH, MIT and Harvard, Cambridge, Massachusetts 02139, USA.|Department of Chemical Engineering, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, USA.|Department of Physics, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, USA.|Institute for Medical Engineering and Science, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, USA.|Department of Chemistry, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, USA.|Department of Biological Engineering, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, USA.
authors.forename: Arup K
authors.initials: AK
authors.lastname: Chakraborty
mesh_terms: D019143:Evolution, Molecular; D005260:Female; D056084:Genetic Fitness; D006678:HIV / Q000235:genetics* / Q000276:immunology; D015658:HIV Infections / Q000276:immunology / Q000821:virology*; D054298:Human Immunodeficiency Virus Proteins / Q000235:genetics*; D006801:Humans; D007111:Immunity, Cellular; D008297:Male; D008957:Models, Genetic; D020815:Polyproteins / Q000235:genetics
chemical_list: D054298:Human Immunodeficiency Virus Proteins; D020815:Polyproteins