The engagement of activating FcγRs inhibits primate lentivirus replication in human macrophages

We previously reported that the stimulation of monocyte-derived macrophages (MDM) by plate-bound i.v. Igs inhibits HIV-1 replication. In this study, we show that IgG immune complexes also suppress HIV-1 replication in MDMs and that activating receptors for the Fc portion of IgG-Fc gamma RI, FcyRIIA, and FcyRIII-are responsible for the inhibition. MDM stimulation through Fc gamma Rs induces activation signals and the secretion of HIV-1 modulatory cytokines, such as M-CSF, TNF-alpha, and macrophage-derived chemokine. However, none of these cytokines contribute to HIV-1 suppression. HIV-1 entry and postintegration steps of viral replication are not affected, whereas reduced levels of reverse transcription products and of integrated proviruses, as determined by real-time PCR analysis, account for the suppression of HIV-1 gene expression in Fc gamma R-activated MDMs. We found that Fc gamma R-dependent activation of MDMs also inhibits the replication of HIV-2, SIVmac, and SIVagm, suggesting a common control mechanism for primate immunodeficiency lentiviruses inactivated macrophages.