Mullins Molecular Retrovirology Lab

  • Department of Microbiology
  • School of Medicine
  • University of Washington
University of Washington/Fred Hutch Center for AIDS Research

Citation Information

Dapp MJ, Kober KM, Chen L, Westfall DH, Wong K, Zhao H, Hall BM, Deng W, Sibley T, Ghorai S, Kim K, Chen N, McHugh S, Au L, Cohen M, Anastos K, Mullins JI (2017). Patterns and rates of viral evolution in HIV-1 subtype B infected females and males. PloS one, 12(10), e0182443. (pubmed) (doi)

Abstract

Biological sex differences affect the course of HIV infection, with untreated women having lower viral loads compared to their male counterparts but, for a given viral load, women have a higher rate of progression to AIDS. However, the vast majority of data on viral evolution, a process that is clearly impacted by host immunity and could be impacted by sex differences, has been derived from men. We conducted an intensive analysis of HIV-1 gag and env-gp120 evolution taken over the first 6-11 years of infection from 8 Women’s Interagency HIV Study (WIHS) participants who had not received combination antiretroviral therapy (ART). This was compared to similar data previously collected from men, with both groups infected with HIV-1 subtype B. Early virus populations in men and women were generally homogenous with no differences in diversity between sexes. No differences in ensuing nucleotide substitution rates were found between the female and male cohorts studied herein. As previously reported for men, time to peak diversity in env-gp120 in women was positively associated with time to CD4+ cell count below 200 (P = 0.017), and the number of predicted N-linked glycosylation sites generally increased over time, followed by a plateau or decline, with the majority of changes localized to the V1-V2 region. These findings strongly suggest that the sex differences in HIV-1 disease progression attributed to immune system composition and sensitivities are not revealed by, nor do they impact, global patterns of viral evolution, the latter of which proceeds similarly in women and men.

Supplemental Data

Supplemental material

Alignments of GAG and ENV:

Sequence ids are pipe-delimited (|) with the following fields:

  • “gnl” (general database reference)
  • “viroverse” (database name)
  • Viroverse accession (Mullins Lab depository)
  • “gb”
  • GenBank accession

The description field of each sequence contains standardized tagged metadata.