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

The β-chemokines RANTES, MIP-1α, and MIP-1β 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 β-chemokines also inhibit the productive infection of monocyte-derived macrophages (MDMs) by a monocytotropic HIV-1 strain, by using virus yield assays. The action of the β-chemokines MIP-1α, MIP-1β, and RANTES was captured with that of the α-chemokine interleukin 8 (IL-8) and of interferon α (IFN-α), which is a well-known broad-range inhibitor of viral replication. While IL-8 did not inhibit HIV-1 BaL replication in MDMs, the β-chemokines were dose-dependently inhibitory. RANTES was the most effective, reaching at 300 ng/ml a protection similar to that obtained with IFN-α at 1000 IU/ml, and was even more inhibitory when added to MDMs after virus attachment. In contrast to IFN-α, the antiviral activity of β- 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.