1. Evolutionary Biology
  2. Microbiology and Infectious Disease
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Mapping mutational effects along the evolutionary landscape of HIV envelope

  1. Hugh K Haddox
  2. Adam S Dingens
  3. Sarah K Hilton
  4. Julie Overbaugh
  5. Jesse D Bloom  Is a corresponding author
  1. Fred Hutchinson Cancer Research Center, United States
Research Article
  • Cited 14
  • Views 2,452
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Cite this article as: eLife 2018;7:e34420 doi: 10.7554/eLife.34420

Abstract

The immediate evolutionary space accessible to HIV is largely determined by how single amino-acid mutations affect fitness. These mutational effects can shift as the virus evolves. However, the prevalence of such shifts in mutational effects remains unclear. Here we quantify the effects on viral growth of all amino-acid mutations to two HIV envelope (Env) proteins that differ at >100 residues. Most mutations similarly affect both Envs, but the amino-acid preferences of a minority of sites have clearly shifted. These shifted sites usually prefer a specific amino acid in one Env, but tolerate many amino acids in the other. Surprisingly, shifts are only slightly enriched at sites that have substituted between the Envs-and many occur at residues that do not even contact substitutions. Therefore, long-range epistasis can unpredictably shift Env's mutational tolerance during HIV evolution, although the amino-acid preferences of most sites are conserved between moderately diverged viral strains.

Article and author information

Author details

  1. Hugh K Haddox

    Basic Sciences Division, Fred Hutchinson Cancer Research Center, Seattle, United States
    Competing interests
    The authors declare that no competing interests exist.
  2. Adam S Dingens

    Basic Sciences Division, Fred Hutchinson Cancer Research Center, Seattle, United States
    Competing interests
    The authors declare that no competing interests exist.
  3. Sarah K Hilton

    Basic Sciences Division, Fred Hutchinson Cancer Research Center, Seattle, United States
    Competing interests
    The authors declare that no competing interests exist.
  4. Julie Overbaugh

    Human Biology Division, Fred Hutchinson Cancer Research Center, Seattle, United States
    Competing interests
    The authors declare that no competing interests exist.
  5. Jesse D Bloom

    Basic Sciences Division, Fred Hutchinson Cancer Research Center, Seattle, United States
    For correspondence
    jbloom@fredhutch.org
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0003-1267-3408

Funding

National Institutes of Health (R01-AI127893)

  • Jesse D Bloom

National Science Foundation (DGE-1256082)

  • Adam S Dingens

Howard Hughes Medical Institute (Faculty Scholar Grant)

  • Jesse D Bloom

Simons Foundation (Faculty Scholar Grant)

  • Jesse D Bloom

Collaboration for AIDS Vaccine Discovery (OPP1111923)

  • Jesse D Bloom

National Institutes of Health (DP1-DA039543)

  • Julie Overbaugh

National Institutes of Health (T32GM007270)

  • Hugh K Haddox

The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.

Reviewing Editor

  1. Arup K Chakraborty, Massachusetts Institute of Technology, United States

Publication history

  1. Received: December 17, 2017
  2. Accepted: March 15, 2018
  3. Accepted Manuscript published: March 28, 2018 (version 1)
  4. Version of Record published: April 20, 2018 (version 2)
  5. Version of Record updated: May 8, 2018 (version 3)

Copyright

© 2018, Haddox et al.

This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.

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