title: 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.
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/mm(2)) than men (mean, 0.44 cells/mm(2); 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.
authors.affiliation: Division of Infectious Diseases, Department of Medicine.
authors.forename: Amie L
authors.initials: AL
authors.lastname: Meditz
authors.forename: Joy M
authors.initials: JM
authors.lastname: Folkvord
authors.forename: Ngan H
authors.initials: NH
authors.lastname: Lyle
authors.forename: Kristina
authors.initials: K
authors.lastname: Searls
authors.forename: Yolanda S
authors.initials: YS
authors.lastname: Lie
authors.forename: Eoin P
authors.initials: EP
authors.lastname: Coakley
authors.forename: Martin
authors.initials: M
authors.lastname: McCarter
authors.forename: Samantha
authors.initials: S
authors.lastname: Mawhinney
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Connick
mesh_terms: D000328:Adult; D015496:CD4-Positive T-Lymphocytes / Q000166:cytology / Q000378:metabolism; D015331:Cohort Studies; D005260:Female; D015658:HIV Infections / Q000276:immunology* / Q000378:metabolism* / Q000821:virology; D006801:Humans; D008198:Lymph Nodes / Q000378:metabolism* / Q000821:virology; D008213:Lymphocyte Activation; D008297:Male; D012367:RNA, Viral / Q000097:blood; D019713:Receptors, CCR5 / Q000096:biosynthesis* / Q000378:metabolism; D012737:Sex Factors; D019562:Viral Load
chemical_list: C584933:CCR5 protein, human; D012367:RNA, Viral; D019713:Receptors, CCR5
keywords: CCR5; HIV-1; Immune activation; Lymph node; Sex differences