Co-evolution networks of HIV/HCV are modular with direct association to structure and function

PLoS Comput Biol. 2018 Sep 7;14(9):e1006409. doi: 10.1371/journal.pcbi.1006409. eCollection 2018 Sep.

Abstract

Mutational correlation patterns found in population-level sequence data for the Human Immunodeficiency Virus (HIV) and the Hepatitis C Virus (HCV) have been demonstrated to be informative of viral fitness. Such patterns can be seen as footprints of the intrinsic functional constraints placed on viral evolution under diverse selective pressures. Here, considering multiple HIV and HCV proteins, we demonstrate that these mutational correlations encode a modular co-evolutionary structure that is tightly linked to the structural and functional properties of the respective proteins. Specifically, by introducing a robust statistical method based on sparse principal component analysis, we identify near-disjoint sets of collectively-correlated residues (sectors) having mostly a one-to-one association to largely distinct structural or functional domains. This suggests that the distinct phenotypic properties of HIV/HCV proteins often give rise to quasi-independent modes of evolution, with each mode involving a sparse and localized network of mutational interactions. Moreover, individual inferred sectors of HIV are shown to carry immunological significance, providing insight for guiding targeted vaccine strategies.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Algorithms
  • Alleles
  • Computational Biology
  • Computer Simulation
  • DNA Mutational Analysis
  • DNA, Viral
  • Disease Progression
  • Evolution, Molecular
  • HIV Core Protein p24 / physiology
  • HIV Infections / virology*
  • HIV-1*
  • HLA Antigens / chemistry
  • Hepacivirus*
  • Hepatitis C / virology*
  • Humans
  • Immune System
  • Normal Distribution
  • Phenotype
  • Principal Component Analysis
  • Protein Domains
  • Structure-Activity Relationship
  • nef Gene Products, Human Immunodeficiency Virus / physiology

Substances

  • DNA, Viral
  • HIV Core Protein p24
  • HLA Antigens
  • nef Gene Products, Human Immunodeficiency Virus

Grants and funding

This work was supported by the General Research Fund of the Hong Kong Research Grants Council (RGC) (grant numbers 16207915, 16234716). AAQ was also supported by the Hong Kong Ph.D. Fellowship Scheme (HKPFS) and MRM by a Hari Harilela endowment. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.