The engagement of activating FcgammaRs 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-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.
David
Annie
A
Unité de Régulations des Infections Rétrovirales, Institut Pasteur, 25 rue du Docteur Roux, 75726 Paris Cedex 15, France.
Sáez-Cirión
Asier
A
Versmisse
Pierre
P
Malbec
Odile
O
Iannascoli
Bruno
B
Herschke
Florence
F
Lucas
Marianne
M
Barré-Sinoussi
Françoise
F
Mouscadet
Jean-François
JF
Daëron
Marc
M
Pancino
Gianfranco
G
D000818:Animals; D002478:Cells, Cultured; D018076:DNA, Complementary / Q000032:analysis; D004279:DNA, Viral / Q000032:analysis; D015497:HIV-1 / Q000502:physiology*; D006801:Humans; D016086:Lentivirus / Q000502:physiology; D008262:Macrophage Activation; D008264:Macrophages / Q000187:drug effects / Q000276:immunology* / Q000821:virology*; D011323:Primates / Q000821:virology; D011533:Proviruses / Q000302:isolation & purification; D017452:Receptors, IgG / Q000819:agonists* / Q000235:genetics; D014779:Virus Replication
D018076:DNA, Complementary; D004279:DNA, Viral; D017452:Receptors, IgG