Compartmentalization of HIV-1 within the female genital tract is due to monotypic and low-diversity variants not distinct viral populations

PLoS One. 2009 Sep 22;4(9):e7122. doi: 10.1371/journal.pone.0007122.

Abstract

Background: Compartmentalization of HIV-1 between the genital tract and blood was noted in half of 57 women included in 12 studies primarily using cell-free virus. To further understand differences between genital tract and blood viruses of women with chronic HIV-1 infection cell-free and cell-associated virus populations were sequenced from these tissues, reasoning that integrated viral DNA includes variants archived from earlier in infection, and provides a greater array of genotypes for comparisons.

Methodology/principal findings: Multiple sequences from single-genome-amplification of HIV-1 RNA and DNA from the genital tract and blood of each woman were compared in a cross-sectional study. Maximum likelihood phylogenies were evaluated for evidence of compartmentalization using four statistical tests. Genital tract and blood HIV-1 appears compartmentalized in 7/13 women by >/=2 statistical analyses. These subjects' phylograms were characterized by low diversity genital-specific viral clades interspersed between clades containing both genital and blood sequences. Many of the genital-specific clades contained monotypic HIV-1 sequences. In 2/7 women, HIV-1 populations were significantly compartmentalized across all four statistical tests; both had low diversity genital tract-only clades. Collapsing monotypic variants into a single sequence diminished the prevalence and extent of compartmentalization. Viral sequences did not demonstrate tissue-specific signature amino acid residues, differential immune selection, or co-receptor usage.

Conclusions/significance: In women with chronic HIV-1 infection multiple identical sequences suggest proliferation of HIV-1-infected cells, and low diversity tissue-specific phylogenetic clades are consistent with bursts of viral replication. These monotypic and tissue-specific viruses provide statistical support for compartmentalization of HIV-1 between the female genital tract and blood. However, the intermingling of these clades with clades comprised of both genital and blood sequences and the absence of tissue-specific genetic features suggests compartmentalization between blood and genital tract may be due to viral replication and proliferation of infected cells, and questions whether HIV-1 in the female genital tract is distinct from blood.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Anti-HIV Agents / therapeutic use
  • Cell-Free System
  • Cross-Sectional Studies
  • DNA, Viral / metabolism
  • Female
  • Genetic Variation
  • Genitalia, Female / virology*
  • Genotype
  • HIV Infections / blood*
  • HIV Infections / virology*
  • HIV-1 / classification*
  • HIV-1 / metabolism*
  • Humans
  • Likelihood Functions
  • Phylogeny
  • RNA, Viral / metabolism
  • Species Specificity

Substances

  • Anti-HIV Agents
  • DNA, Viral
  • RNA, Viral