HIV-1 Chemokine Coreceptor Utilization in Paired Cerebrospinal Fluid and Plasma Samples: A Survey of Subjects With Viremia

J Infect Dis. 2005 Mar 15;191(6):890-8. doi: 10.1086/428095. Epub 2005 Feb 9.

Abstract

Background: Chemokine receptors serve as coreceptors for human immunodeficiency virus type 1 (HIV-1) entry, influence cell tropism, and may critically determine central nervous system infection pathogenesis. Using an in vitro functional entry assay, we examined utilization of 2 principal coreceptors in cerebrospinal fluid (CSF) and plasma in 46 subjects.

Methods: Paired CSF and plasma samples were selected from subjects with a range of CD4 T cell counts. Amplified populations of env sequences were characterized as using CCR5 (R5), CXCR4 (X4), or both receptors (R5+X4). Individual clones derived from 3 subjects were analyzed for viral tropism and phylogeny.

Results: CSF and plasma pairs were mainly concordant for R5 (36/46) or R5+X4 (5/46) viruses. However, 5 pairs were discordant, 2 of which had the R5+X4 phenotype in CSF despite having the R5 phenotype in plasma. Although R5+X4 tropism was associated with advanced immunodeficiency, all 4 subjects with acquired immunodeficiency syndrome dementia complex had R5 tropism in CSF. Clones derived from R5+X4-tropic populations revealed mixtures of R5 and X4 viruses and viruses able to utilize either coreceptor, suggesting both virus exchange between compartments and autonomous CSF virus evolution.

Conclusions: Although R5 viruses predominate in the CSF, HIV-1 populations able to utilize CXCR4 are also present. Discordant tropism in CSF and plasma may have implications for R5 inhibitor therapy.

Publication types

  • Clinical Trial
  • Comparative Study
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • AIDS Dementia Complex / drug therapy
  • AIDS Dementia Complex / virology
  • Adult
  • Anti-HIV Agents / therapeutic use
  • Blood / virology*
  • CD4 Lymphocyte Count
  • Cerebrospinal Fluid / virology*
  • Cohort Studies
  • Cross-Sectional Studies
  • Female
  • Gene Products, env / genetics
  • HIV Infections / drug therapy
  • HIV Infections / virology
  • HIV-1 / genetics
  • HIV-1 / metabolism
  • HIV-1 / pathogenicity*
  • Humans
  • Longitudinal Studies
  • Male
  • Phylogeny
  • RNA, Viral / blood
  • Receptors, CCR5 / metabolism*
  • Receptors, CXCR4 / metabolism*
  • Viremia / virology*

Substances

  • Anti-HIV Agents
  • Gene Products, env
  • RNA, Viral
  • Receptors, CCR5
  • Receptors, CXCR4