CCR5 expression is reduced in lymph nodes of HIV type 1-infected women, compared with men, but does not mediate sex-based differences in viral loads

Amie L. Meditz, Joy M. Folkvord, Ngan H. Lyle, Kristina Searls, Yolanda S. Lie, Eoin P. Coakley, Martin McCarter, Samantha Mawhinney, Elizabeth Connick

Research output: Contribution to journalArticlepeer-review

8 Scopus citations

Abstract

Background. Human immunodeficiency virus type 1 (HIV-1)-infected women have lower viral loads than men but similar rates of disease progression. We hypothesized that sex-based differences in CCR5 expression mediate viral load differences.Methods. CCR5 was analyzed by flow cytometry in disaggregated lymph node cells from untreated HIV-1-infected women (n = 28) and men (n = 27). The frequencies of HIV-1 RNA-producing cells in the lymph node were determined by in situ hybridization. Linear and generalized linear regression models were used.Results. The percentage of CCR5+CD3+CD4+ cells was lower in women (mean, 12%) than men (mean, 16%; P =. 034). Neither the percentage of CCR5+CD3+CD4+ cells nor the CCR5 density predicted viral load or HIV-1 RNA-producing lymph node cells (P ≥. 24), after adjusting for CD4+ T-cell count, race, and age. Women had marginally fewer HIV-1 RNA-producing cells (mean, 0.21 cells/mm2) than men (mean, 0.44 cells/mm2; P =. 046). After adjusting for the frequency of HIV-1 RNA-producing cells and potential confounders, the viral load in women were 0.46 log10 copies/mL lower than that in men (P =. 018).Conclusions. Reduced lymph node CCR5 expression in women did not account for the viral load difference between sexes. CCR5 expression did not predict viral load or frequencies of HIV-1 RNA-producing cells, indicating that physiologic levels of CCR5 do not limit HIV-1 replication in lymph node. Less plasma virus was associated with each HIV-1 RNA-producing cell in women as compared to men, suggesting that women may either produce fewer virions per productively infected cell or more effectively clear extracellular virus.

Original languageEnglish (US)
Pages (from-to)922-930
Number of pages9
JournalJournal of Infectious Diseases
Volume209
Issue number6
DOIs
StatePublished - Mar 2014
Externally publishedYes

Keywords

  • CCR5
  • HIV-1
  • Immune activation
  • Lymph node
  • Sex differences

ASJC Scopus subject areas

  • Immunology and Allergy
  • Infectious Diseases

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