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Mapping mutational effects along the evolutionary landscape of HIV envelope.

Hugh K Haddox | Adam S Dingens | Sarah K Hilton | Julie Overbaugh | Jesse D Bloom
eLife | 2018

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 [Formula: see text]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.

Pubmed ID: 29590010

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None found

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Associated grants

  • Agency: NIDA NIH HHS, United States
    Id: DP1 DA039543
  • Agency: NIGMS NIH HHS, United States
    Id: T32 GM007270
  • Agency: NIAID NIH HHS, United States
    Id: R01 AI127893
  • Agency: NIH HHS, United States
    Id: R01-AI127893
  • Agency: NIGMS NIH HHS, United States
    Id: R01 GM102198
  • Agency: NIH HHS, United States
    Id: T32GM007270
  • Agency: Howard Hughes Medical Institute, United States
    Id: Faculty Scholar Grant
  • Agency: NIGMS NIH HHS, United States
    Id: T32 GM008268
  • Agency: NIH HHS, United States
    Id: DP1-DA039543

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