Inhibition of HIV type 1 BaL replication by MIP-1α, MIP-1β, and RANTES in macrophages

The beta-chemokines RANTES, MIP-1 alpha, and MIP-1 beta have been shown to inhibit the infection of T cells by macrophage-tropic HIV-1 strains by blocking env-driven HIV-1 fusion through competition for the chemokine receptors or receptor downregulation, This study was aimed at testing whether beta-chemokines also inhibit the productive infection of monocyte-derived macrophages (MDMs) by a monocytotropic HIV-I strain, by using virus yield assays, The action of the beta-chemokines MIP-1 alpha; MIP-1 beta, and RANTES was captured with that of the alpha-chemokine interleukin 8 (IL-8) and of interferon alpha (IFN-alpha), which is a well-known broad-range inhibitor of viral replication, While IL-8 did not inhibit HIV-1 BaL replication in MDMs, the beta-chemokines were dose-dependently inhibitory, RANTES was the most effective, reaching at 300 ng/ml a protection similar to that obtained with IFN-alpha at 1000 IU/ml, and was even more inhibitory when added to MDMs after virus attachment, In contrast to IFN-alpha, the antiviral activity of beta-chemokines was restricted to HIV, because another virus was not inhibited, As compared with untreated MDMs, full-length proviral DNA at day 1 postinfection was inhibited in MDMs treated with RANTES either before or after the absorption phase, and even more so in IFN-treated MDMs, whereas in IL-8-treated MDMs no inhibition was observed, Our results indicate that in MDMs both RANTES and IFN affect early steps of HIV-1 BaL replication, preceding the completion of viral DNA synthesis.