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

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Listed:
  • John P. Barton

    (Ragon Institute of MGH, MIT and Harvard
    Massachusetts Institute of Technology
    Massachusetts Institute of Technology
    Institute for Medical Engineering and Science, Massachusetts Institute of Technology)

  • Nilu Goonetilleke

    (Immunology and Medicine, University of North Carolina
    University of Oxford)

  • Thomas C. Butler

    (Massachusetts Institute of Technology
    Massachusetts Institute of Technology)

  • Bruce D. Walker

    (Ragon Institute of MGH, MIT and Harvard
    Howard Hughes Medical Institute)

  • Andrew J. McMichael

    (University of Oxford)

  • Arup K. Chakraborty

    (Ragon Institute of MGH, MIT and Harvard
    Massachusetts Institute of Technology
    Massachusetts Institute of Technology
    Institute for Medical Engineering and Science, Massachusetts Institute of Technology)

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.

Suggested Citation

  • John P. Barton & Nilu Goonetilleke & Thomas C. Butler & Bruce D. Walker & Andrew J. McMichael & Arup K. Chakraborty, 2016. "Relative rate and location of intra-host HIV evolution to evade cellular immunity are predictable," Nature Communications, Nature, vol. 7(1), pages 1-10, September.
    • Handle: RePEc:nat:natcom:v:7:y:2016:i:1:d:10.1038_ncomms11660
    DOI: 10.1038/ncomms11660
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    Cited by:

    1. Ahmed Abdul Quadeer & David Morales-Jimenez & Matthew R McKay, 2018. "Co-evolution networks of HIV/HCV are modular with direct association to structure and function," PLOS Computational Biology, Public Library of Science, vol. 14(9), pages 1-29, September.
    2. Hang Zhang & Ahmed Abdul Quadeer & Matthew R. McKay, 2023. "Direct-acting antiviral resistance of Hepatitis C virus is promoted by epistasis," Nature Communications, Nature, vol. 14(1), pages 1-14, December.

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