Antibody-enhanced infection by HIV-1 via Fc receptor-mediated entry.
Monocytes and macrophages, which may play a central role in the pathogenesis of infection with human immunodeficiency virus type 1 (HIV-1), express the CD4 molecule and Fc receptors (FcR) for immunoglobulin G (IgG). To explore the possibility that FcR mediate HIV-1 infection of monocytes, studies were conducted with the human monocytic cell line U937. These cells were exposed to HIV-1 complexed with various concentrations of serum from HIV-1 antibody-positive individuals and monitored for HIV-1 replication. Serum samples from antibody-negative normal individuals did not affect virus yields. High concentrations of antibody-positive sera showed virus-neutralizing activity; however, cells infected with HIV-1 in the presence of antibody-positive sera at subneutralizing concentrations significantly enhanced virus replication. This infection enhancement was blocked by heat-aggregated gamma-globulin. Moreover, the IgG fraction from an HIV-1 antibody-positive serum enhanced HIV-1 infection at the same serum dilution equivalents. In contrast, IgG-F(ab')2 did not enhance HIV-1 infection but showed neutralizing activity with HIV-1. These results are compatible with the concept of FcR-mediated infection enhancement and suggest that this immunological response to HIV-1, instead of protecting the host, potentially facilitates the infection.
Takeda
A
A
Department of Medicine, University of Massachusetts Medical School, Worcester 01655.
Tuazon
C U
CU
Ennis
F A
FA
D000163:Acquired Immunodeficiency Syndrome / Q000276:immunology / Q000382:microbiology*; D000936:Antigen-Antibody Complex; D000943:Antigens, Differentiation / Q000502:physiology*; D002460:Cell Line; D015483:HIV Antibodies / Q000276:immunology*; D015497:HIV-1 / Q000276:immunology / Q000472:pathogenicity*; D006801:Humans; D066298:In Vitro Techniques; D009000:Monocytes / Q000382:microbiology*; D011961:Receptors, Fc / Q000502:physiology*; D017452:Receptors, IgG
D000936:Antigen-Antibody Complex; D000943:Antigens, Differentiation; D015483:HIV Antibodies; D011961:Receptors, Fc; D017452:Receptors, IgG