Involvement of Fc gamma RI (CD64) in the mechanism of HIV-1 inhibition by polyclonal IgG purified from infected patients in cultured monocyte-derived macrophages.
The aim of this study was to investigate the mechanism of HIV-1 neutralization using monocyte-derived macrophages (MDM) in comparison to PBMC as target cells. For this purpose, we analyzed neutralizing activities of different human polyclonal IgG samples purified from sera of HIV-1-infected individuals using a single cycle infection assay. We found an increase of the neutralizing titer when macrophages vs PBMC were used as target cells. Moreover, polyclonal IgG from HIV-1-infected patients that are not able to neutralize virus when PBMC are used as target cells strongly inhibit MDM infection. Similar results were obtained with neutralizing mAbs. To explore the participation of FcgammaRs in HIV-1 inhibition, F(ab')(2) and Fab of these Igs were produced. Results indicated that both F(ab')(2) and Fab are less effective to inhibit virus replication in MDM. Moreover, competition experiments with Fc fragments of IgG from healthy donors or with purified monoclonal anti-human FcgammaRs Ab strengthen the participation of the FcgammaRs, and in particular of FcgammaRI (CD64) in HIV-1 inhibition on MDM. Mechanisms by which HIV-specific IgG inhibit virus replication in cultured macrophages are proposed and the benefit of inducing such Abs by vaccination is discussed.
Holl
Vincent
V
Equipe d'Accueil 3770, Université Louis Pasteur (ULP), Institut de Virologie, 3 rue Koeberlé, 67000 Strasbourg, France. Vincent.Holl@hemato-ulp.u-strasbg.fr
Hemmerter
Stéphane
S
Burrer
Renaud
R
Schmidt
Sylvie
S
Bohbot
Alain
A
Aubertin
Anne-Marie
AM
Moog
Christiane
C
D019380:Anti-HIV Agents / Q000494:pharmacology; D000998:Antiviral Agents / Q000502:physiology*; D001667:Binding, Competitive / Q000276:immunology; D002478:Cells, Cultured; D018925:Chemokines / Q000096:biosynthesis; D015658:HIV Infections / Q000276:immunology*; D015497:HIV-1 / Q000276:immunology*; D006801:Humans; D007070:Immunoglobulin A / Q000302:isolation & purification / Q000502:physiology; D007140:Immunoglobulin Fab Fragments / Q000302:isolation & purification / Q000502:physiology; D007074:Immunoglobulin G / Q000096:biosynthesis / Q000302:isolation & purification* / Q000502:physiology*; D008264:Macrophages / Q000276:immunology* / Q000378:metabolism* / Q000821:virology; D009000:Monocytes / Q000276:immunology / Q000378:metabolism / Q000821:virology; D009500:Neutralization Tests; D010587:Phagocytosis / Q000276:immunology; D011485:Protein Binding / Q000276:immunology; D017452:Receptors, IgG / Q000276:immunology / Q000378:metabolism / Q000502:physiology*; D014779:Virus Replication / Q000276:immunology
D019380:Anti-HIV Agents; D000998:Antiviral Agents; D018925:Chemokines; D007070:Immunoglobulin A; D007140:Immunoglobulin Fab Fragments; D007074:Immunoglobulin G; D017452:Receptors, IgG