Coreceptor tropism in human immunodeficiency virus type 1 subtype D: high prevalence of CXCR4 tropism and heterogeneous composition of viral populations

J Virol. 2007 Aug;81(15):7885-93. doi: 10.1128/JVI.00218-07. Epub 2007 May 16.

Abstract

In human immunodeficiency virus type 1 (HIV-1) subtype B, CXCR4 coreceptor use ranges from approximately 20% in early infection to approximately 50% in advanced disease. Coreceptor use by non-subtype B HIV is less well characterized. We studied coreceptor tropism of subtype A and D HIV-1 collected from 68 pregnant, antiretroviral drug-naive Ugandan women (HIVNET 012 trial). None of 33 subtype A or 10 A/D-recombinant viruses used the CXCR4 coreceptor. In contrast, nine (36%) of 25 subtype D viruses used both CXCR4 and CCR5 coreceptors. Clonal analyses of the nine subtype D samples with dual or mixed tropism revealed heterogeneous viral populations comprised of X4-, R5-, and dual-tropic HIV-1 variants. In five of the six samples with dual-tropic strains, V3 loop sequences of dual-tropic clones were identical to those of cocirculating R5-tropic clones, indicating the presence of CXCR4 tropism determinants outside of the V3 loop. These dual-tropic variants with R5-tropic-like V3 loops, which we designated "dual-R," use CCR5 much more efficiently than CXCR4, in contrast to dual-tropic clones with X4-tropic-like V3 loops ("dual-X"). These observations have implications for pathogenesis and treatment of subtype D-infected individuals, for the association between V3 sequence and coreceptor tropism phenotype, and for understanding potential mechanisms of evolution from exclusive CCR5 use to efficient CXCR4 use by subtype D HIV-1.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Algorithms
  • Amino Acid Sequence
  • Female
  • Gene Products, env / genetics
  • Gene Products, env / metabolism
  • Genetic Variation
  • HIV Infections / virology
  • HIV-1 / immunology
  • HIV-1 / pathogenicity
  • HIV-1 / physiology*
  • Humans
  • Phenotype
  • Phylogeny
  • Pregnancy
  • Pregnancy Complications, Infectious / virology
  • Receptors, CCR5 / genetics
  • Receptors, CCR5 / metabolism
  • Receptors, CXCR4 / genetics
  • Receptors, CXCR4 / metabolism*
  • Viral Load

Substances

  • Gene Products, env
  • Receptors, CCR5
  • Receptors, CXCR4