Effect of RANTES on the infection of monocyte-derived primary macrophages by human immunodeficiency virus type 1 and type 2

The effect of beta chemokines on human immunodeficiency virus type 1 (HIV-1 ) infection of primary macrophages is controversial, and their effect on HI V-2 infection of these cells has not yet been documented. We examined the e ffect of synthetic and recombinant regulated-on-activation, normal T cell-e xpressed and -secreted (RANTES) on HIV-1 and HIV-2 infection of primary mon ocyte-derived-macrophages (MDM) that were obtained as the adherent cells of 5-day cultures of blood mononuclear cells (PBMC), followed by 2-day cultur e without peripheral blood mononuclear cells (PBMCs) nor added cytokines. T hese MDM expressed CD4, CCR5 and CXCR4, the major coreceptors for HIV macro phage- and T cell-tropic isolates, respectively. Infection of MDM from diff erent donors with HIV-1 or HIV-2 macrophage-tropic strains was reproducibly inhibited by RANTES. This inhibition depended on RANTES continuous presenc e in culture during and after infection. Treatment of MDM with RANTES just before or during, but not after, exposure to virus did nor protect MDM from infection. When RANTES was added after MDM had been infected, and was cont inuously maintained in culture thereafter, no inhibition occurred and limit ed enhancement of infection could be observed. These data indicate that RAN TES inhibits HIV-1 as well as HIV-2 infection of MDM, likely at a post-bind ing step, and support the role of CCR5 as the major coreceptor for HIV-1 an d HIV-2 entry into primary macrophages. (C) 1998 Elsevier, Paris.