title: CC chemokine receptor 5 cell-surface expression in relation to CC chemokine receptor 5 genotype and the clinical course of HIV-1 infection.
abstract: CCR5 cell-surface expression was studied in relation to CCR5 genotype and clinical course of HIV-1 infection. HIV-1 infected CCR5+/+ individuals had higher percentages of CCR5-expressing CD4+ T cells as compared with HIV-1-infected CCR532/+ individuals. For both genotypic groups, the percentages of CCR5-expressing cells were higher than for the uninfected counterparts (CCR5+/+, HIV+ 28% and HIV- 15% (p < 0.0001); CCR532/+, HIV+ 21% and HIV- 10% (p = 0.001), respectively). In HIV-1-infected individuals, high percentages of CCR5-expressing cells were associated with low CD4+ T cell numbers (p = 0.001), high viral RNA load in serum (p = 0.046), and low T cell function (p = 0.054). As compared with nonprogressors with similar CD4+ T cell numbers, individuals who did progress to AIDS had a higher percentage of CCR5-expressing CD4+ T cells (32% vs 21% (p = 0.002). Longitudinal analysis of CCR5+/+ individuals revealed slight, although not statistically significant, increases in CCR5-expressing CD4+ T cells and CD4+ T cell subsets characterized by the expression of CD45 isoforms, during the course of HIV-1 infection. Preseroconversion, the percentage of CCR5-expressing CD4+ T cells was higher in individuals who subsequently developed AIDS (28%) than in those who did not show disease progression within a similar time frame (20%; p = 0.059). Our data indicate that CCR5 expression increases with progression of disease, possibly as a consequence of continuous immune activation associated with HIV-1 infection. In turn, CCR5 expression may influence the clinical course of infection.
authors.affiliation: Department of Clinical Viro-Immunology, Central Laboratory of the Red Cross Blood Transfusion Service, Amsterdam, The Netherlands.
authors.forename: A M
authors.initials: AM
authors.lastname: de Roda Husman
authors.forename: H
authors.initials: H
authors.lastname: Blaak
authors.forename: M
authors.initials: M
authors.lastname: Brouwer
authors.forename: H
authors.initials: H
authors.lastname: Schuitemaker
mesh_terms: D000328:Adult; D018791:CD4 Lymphocyte Count; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology / Q000378:metabolism; D002462:Cell Membrane / Q000276:immunology / Q000378:metabolism; D003430:Cross-Sectional Studies; D018450:Disease Progression; D005838:Genotype; D015658:HIV Infections / Q000097:blood / Q000235:genetics* / Q000276:immunology* / Q000821:virology; D015497:HIV-1 / Q000276:immunology*; D006801:Humans; D008137:Longitudinal Studies; D008297:Male; D019713:Receptors, CCR5 / Q000096:biosynthesis* / Q000235:genetics*; D019718:Receptors, CXCR4 / Q000096:biosynthesis; D016176:T-Lymphocyte Subsets / Q000276:immunology / Q000378:metabolism; D019562:Viral Load
chemical_list: D019713:Receptors, CCR5; D019718:Receptors, CXCR4