Identification of HIV-1 genitourinary tract compartmentalization by analyzing the env gene sequences in urine

AIDS. 2015 Aug 24;29(13):1651-7. doi: 10.1097/QAD.0000000000000757.

Abstract

Objective: HIV-1 persists indefinitely in memory CD4 T cells and other long-lived cellular reservoirs despite antiretroviral therapy. Our group had previously demonstrated that HIV-1 can establish a productive infection in renal epithelial cells and that the kidney represents a separate compartment for HIV-1 replication. Here, to better understand the viruses in this unique site, we genetically characterized and compared the viruses in blood and urine specimens from 24 HIV-1 infected patients with detectable viremia.

Design and methods: Blood and urine samples were obtained from 35 HIV-1 positive patients. Single-genome amplification was performed on HIV-1 env RNA and DNA isolated from urine supernatants and urine-derived cell pellets, respectively, as well as from plasma and peripheral blood mononuclear cell from the same individuals. Neighbor-joining trees were constructed under the Kimura 2-parameter model.

Results: We amplified and sequenced the full-length HIV-1 envelope (env) gene from 12 of the 24 individuals, indicating that 50% of the viremic HIV-1-positive patients had viral RNA in their urine. Phylogenetic analysis of the env sequences from four individuals with more than 15 urine-derived env sequences showed that the majority of the sequences from urine formed distinct cluster(s) independent of those peripheral blood mononuclear cell and plasma-derived sequences, consistent with viral compartmentalization in the urine.

Conclusion: Our results suggest the presence of a distinct HIV compartment in the genitourinary tract.

Publication types

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

MeSH terms

  • Blood / virology
  • DNA, Viral / urine
  • Female
  • Gene Products, env / genetics*
  • Genetic Variation
  • HIV Infections / virology*
  • HIV-1 / classification
  • HIV-1 / genetics
  • HIV-1 / isolation & purification*
  • Humans
  • Leukocytes, Mononuclear / virology
  • Male
  • Polymerase Chain Reaction
  • RNA, Viral / urine
  • Sequence Analysis, DNA
  • Urinary Tract Infections / virology*
  • Urine / virology*

Substances

  • DNA, Viral
  • Gene Products, env
  • RNA, Viral