The engagement of activating FcgammaRs inhibits primate lentivirus replication in human macrophages.

Annie David (1) , Asier Sáez-Cirión (1) , Pierre Versmisse (1) , Odile Malbec (2) , Bruno Iannascoli (2) , Florence Herschke (1) , Marianne Lucas (3) , Françoise Barré-Sinoussi (1) , Jean-François Mouscadet (4) , Marc Daëron (2) , Gianfranco Pancino (1)

1 Régulation des Infections Rétrovirales
2 Allergologie Moléculaire et Cellulaire
3 Interactions Moléculaires Flavivirus-Hôtes
4 LBPA - Laboratoire de Biologie et de Pharmacologie Appliquée

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-FcgammaRI, FcgammaRIIA, and FcgammaRIII-are responsible for the inhibition. MDM stimulation through FcgammaRs 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 FcgammaR-activated MDMs. We found that FcgammaR-dependent activation of MDMs also inhibits the replication of HIV-2, SIVmac, and SIVagm, suggesting a common control mechanism for primate immunodeficiency lentiviruses in activated macrophages.

Domaines: Maladies infectieuses

Annie David, Asier Sáez-Cirión, Pierre Versmisse, Odile Malbec, Bruno Iannascoli, et al.. The engagement of activating FcgammaRs inhibits primate lentivirus replication in human macrophages.. Journal of Immunology, 2006, 177 (9), pp.6291-300. ⟨10.4049/jimmunol.177.9.6291⟩. ⟨pasteur-00167539⟩