No difference in in vitro susceptibility to HIV type 1 between high-risk HIV-negative Ethiopian commercial sex workers and low-risk control subjects

AIDS Res Hum Retroviruses. 2001 Mar 20;17(5):433-41. doi: 10.1089/088922201750102526.

Abstract

Host factors such as increased beta-chemokine production, HIV-1 coreceptor expression level, and HIV-1 coreceptor polymorphism have been thought to influence susceptibility to HIV-1 infection. To determine the protective role of these factors in Ethiopians who remained HIV-1 uninfected, despite multiple high-risk sexual exposures, we studied 21 Ethiopian women who had been employed as commercial sex workers (CSWs) for five or more years. The HIV-1-resistant CSWs were compared with low-risk age-matched female controls who had a comparable CD4+ cell percentage and mean fluorescence intensity (MFI). Genetic polymorphism in the CCR5, CCR2b, or SDF-1 genes appeared not to be associated with resistance in the Ethiopian CSWs. Expression levels of CCR5 and CXCR4 on naive, memory, and total CD4+ T cells tended to be higher in the resistant CSWs, while the production of beta-chemokines RANTES, MIP-1alpha, and MIP-1beta by phytohemagglutinin (PHA)-stimulated peripheral blood mononuclear cells (PBMCs) was lower compared with low-risk HIV-1 negative controls. In vitro susceptibility of PHA-stimulated PBMCs to primary, CCR5-restricted, Ethiopian HIV-1 isolates was comparable between resistant CSWs and low-risk controls. In vitro susceptibility was positively correlated to CD4+ cell mean fluorescence intensity and negatively correlated to CCR5 expression levels, suggesting that infection of PBMCs was primarily dependent on expression levels of CD4 and that CCR5 expression, above a certain threshold, did not further increase susceptibility. Our results show that coreceptor polymorphism, coreceptor expression levels, beta-chemokine production, and cellular resistance to in vitro HIV-1 infection are not associated with protection in high-risk HIV-1-negative Ethiopian CSWs.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • CD4 Lymphocyte Count
  • Chemokines, CC / metabolism
  • Chemokines, CC / pharmacology
  • Cohort Studies
  • Disease Susceptibility
  • Ethiopia
  • Female
  • Flow Cytometry
  • HIV Seronegativity*
  • HIV-1 / immunology*
  • Humans
  • In Vitro Techniques
  • Middle Aged
  • Polymorphism, Genetic
  • Receptors, CCR5 / genetics
  • Receptors, CCR5 / metabolism
  • Receptors, Cytokine / metabolism
  • Risk Factors
  • Sex Work*

Substances

  • Chemokines, CC
  • Receptors, CCR5
  • Receptors, Cytokine