Immune activation in Africa is environmentally-driven and is associated with upregulation of CCR5

Background: HIV infection in Africa is associated with immune activation an d a cytokine profile that stimulates CCR5 expression. We investigated wheth er this immune activation is environmentally driven; if a dominant expressi on of CCR5 could indeed be detected in African individuals; and if R5 HIV s trains would be prevalent in this population. Methods: Freshly drawn peripheral blood mononuclear cells from HIV-uninfect ed African and Italian individuals living in rural Africa, from HIV-uninfec ted Africans and Italians living in Italy, and from HIV-infected African an d Italian patients were analysed. Determinations of HIV coreceptor-specific mRNAs and immunophenotype analyses were performed in all samples. Virologi cal analyses included virus isolation and characterization of plasma neutra lizing activity. Findings: Results showed that: immune activation is detected both in Italia n and African HIV-uninfected individuals living in Africa but not in Africa n subjects living in Italy; CCR5-specific mRNA is augmented and the surface expression of CCR5 is increased in African compared with Italian residents (CXCR4-specific mRNA is comparable); R5-HIV strains are isolated prevalent ly from lymphocytes of African HIV-infected patients; and plasma neutralizi ng activity in HIV-infected African patients is mostly specific for R5 stra ins. Conclusions: Immune activation in African residents is environmentally driv en and not genetically predetermined. This immune activation results in a s kewing of the CCR5 : CXCR4 ratio which is associated with a prevalent isola tion of R5 viruses. These data suggest that the selection of the predominan t virus strain within the population could be influenced by an immunologica lly driven pattern of HIV co receptor expression. (C) 2000 Lippincott Willi ams & Wilkins.