Immune activation in Africa is environmentally-driven and... : AIDS (original) (raw)

Basic Science

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

Clerici, Mario; Butto, Stefanoa; Lukwiya, Matthewb; Saresella, Marinac; Declich, Silviad; Trabattoni, Daria; Pastori, Claudiae; Piconi, Stefaniaf; Fracasso, Claudioa; Fabiani, Massimod; Ferrante, Pasqualeg; Rizzardini, Giulianof; Lopalco, Luciae for the Italian–Ugandan AIDS Project

From the Cattedra di Immunologia, Universita di Milano, Milano, the aLaboratorio di Virologia, Istituto Superiore di Sanita, Roma, bSt. Mary's Hospital Lacor, Gulu, Uganda, cLaboratorio di Biologia, Università di Milano, Don C. Gnocchi Foundation, IRCCS, Milano, dLaboratorio di Epidemiologia, Istituto Superiore di Sanita, Roma, eDIBIT San Raffaele Scientific Institute, fIa Divisione di Malattie Infettive, H. Luigi Sacco, Milano and gCattedra di Virologia, Università di Milano, Don C. Gnocchi Foundation, IRCCS, Milano, Italy.

Received: 8 December 1999;

revised: 17 April 2000; accepted: 2 June 2000.

Sponsorship: Supported by grants from Istituto Superiore di Sanita ‘X Progetto AIDS’ and ‘Uganda AIDS Project no. 667'.

Requests for reprints to: M. Clerici, Cattedra di Immunologia, Universita’ degli Studi di Milano, DISP LITA Vialba; Via GB. Grassi, 74, 20157 Milano, Italy.

Abstract

Background

HIV infection in Africa is associated with immune activation and a cytokine profile that stimulates CCR5 expression. We investigated whether this immune activation is environmentally driven; if a dominant expression of CCR5 could indeed be detected in African individuals; and if R5 HIV strains would be prevalent in this population.

Methods

Freshly drawn peripheral blood mononuclear cells from HIV-uninfected African and Italian individuals living in rural Africa, from HIV-uninfected Africans and Italians living in Italy, and from HIV-infected African and Italian patients were analysed. Determinations of HIV coreceptor-specific mRNAs and immunophenotype analyses were performed in all samples. Virological analyses included virus isolation and characterization of plasma neutralizing activity.

Findings

Results showed that: immune activation is detected both in Italian and African HIV-uninfected individuals living in Africa but not in African 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 prevalently from lymphocytes of African HIV-infected patients; and plasma neutralizing activity in HIV-infected African patients is mostly specific for R5 strains.

Conclusions

Immune activation in African residents is environmentally driven and not genetically predetermined. This immune activation results in a skewing of the CCR5 : CXCR4 ratio which is associated with a prevalent isolation of R5 viruses. These data suggest that the selection of the predominant virus strain within the population could be influenced by an immunologically driven pattern of HIV co receptor expression.