Human Immunodeficiency Viruses Appear Compartmentalized to the Female Genital Tract in Cross-Sectional Analyses but Genital Lineages Do Not Persist Over Time

J Infect Dis. 2013 Apr 15;207(8):1206-15. doi: 10.1093/infdis/jit016. Epub 2013 Jan 11.

Abstract

Background: Whether unique human immunodeficiency type 1 (HIV) genotypes occur in the genital tract is important for vaccine development and management of drug resistant viruses. Multiple cross-sectional studies suggest HIV is compartmentalized within the female genital tract. We hypothesize that bursts of HIV replication and/or proliferation of infected cells captured in cross-sectional analyses drive compartmentalization but over time genital-specific viral lineages do not form; rather viruses mix between genital tract and blood.

Methods: Eight women with ongoing HIV replication were studied during a period of 1.5 to 4.5 years. Multiple viral sequences were derived by single-genome amplification of the HIV C2-V5 region of env from genital secretions and blood plasma. Maximum likelihood phylogenies were evaluated for compartmentalization using 4 statistical tests.

Results: In cross-sectional analyses compartmentalization of genital from blood viruses was detected in three of eight women by all tests; this was associated with tissue specific clades containing multiple monotypic sequences. In longitudinal analysis, the tissues-specific clades did not persist to form viral lineages. Rather, across women, HIV lineages were comprised of both genital tract and blood sequences.

Conclusions: The observation of genital-specific HIV clades only in cross-sectional analysis and an absence of genital-specific lineages in longitudinal analyses suggest a dynamic interchange of HIV variants between the female genital tract and blood.

Publication types

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

MeSH terms

  • Cross-Sectional Studies
  • Female
  • Genes, Viral
  • Genitalia, Female / virology*
  • Genotype
  • Glycosylation
  • HIV Infections / blood*
  • HIV Infections / pathology
  • HIV Infections / virology
  • HIV-1 / genetics
  • HIV-1 / pathogenicity*
  • HIV-1 / physiology
  • Humans
  • Likelihood Functions
  • Longitudinal Studies
  • Phylogeny
  • RNA, Viral / analysis
  • RNA, Viral / genetics
  • Reproductive Tract Infections / blood
  • Reproductive Tract Infections / pathology
  • Reproductive Tract Infections / virology
  • Sequence Analysis, RNA
  • Species Specificity
  • Time Factors
  • Virus Replication
  • env Gene Products, Human Immunodeficiency Virus / blood
  • env Gene Products, Human Immunodeficiency Virus / genetics*
  • env Gene Products, Human Immunodeficiency Virus / metabolism

Substances

  • RNA, Viral
  • env Gene Products, Human Immunodeficiency Virus