EXPRESSION OF CHEMOKINE RECEPTORS CXCR4 AND CCR5 IN HIV-1-INFECTED AND UNINFECTED INDIVIDUALS

The chemokine receptors CXCR4 and CCR5 have been identified as major c oreceptors for HIV-1 entry into CD4(+) T cells. The majority of primar y HIV-1 isolates in early disease use CCR5 as a coreceptor, whereas du ring disease progression with the emergence pf syncytium-inducing viru ses, CXCR4 is also used. We performed a cross-sectional study in which we evaluated the expression of two HIV-1 coreceptors, CCR5 and CXCR4, in whole blood samples taken from HIV-1-infected and uninfected indiv iduals. We demonstrate that CXCR4 on CD4(+) and CD8(+) T cells, and CD 14(+) monocytes is significantly down-regulated, and CCR5 expression o n CD4(+) T cells is up-regulated in HIV-infected individuals compared with uninfected controls. Coreceptor expression correlated with the le vel of cellular activation in vivo in both HIV-infected and uninfected individuals, with CXCR4 being expressed predominantly on quiescent (H LA-DR-) T cells and CCR5 being expressed predominantly on activated (H LA-DR+) T cells, Lower expression of CXCR4 and higher expression of CC R5 on CD4(+) T cells correlated with advancing disease. In addition, a tendency for greater activation of CXCR4(+)CD4(+) T cells in patients with advanced disease was observed. Patients who harbored syncytium-i nducing viruses, however, could not be distinguished from those who ha rbored nonsyncytium-inducing viruses based on the level of CD4(+) T ce ll activation or chemokine receptor expression.