Two receptors are required for antibody-dependent enhancement of human immunodeficiency virus type 1 infection: CD4 and Fc gamma R.
Evidence of antibody-dependent enhancement of human immunodeficiency virus type 1 (HIV-1) infection via Fc receptor (FcR) was published previously (A. Takeda, C. U. Tuazon, and F. A. Ennis, Science 242:580-583, 1988). To define the entry mechanism of HIV-1 complexed with anti-HIV-1 antibody, we attempted to determine the receptor molecules responsible for mediating enhancement of HIV-1 infection of monocytic cells. Monoclonal antibodies to FcRI for immunoglobulin G substantially blocked antibody-dependent enhancement of HIV-1 infection. Furthermore, we demonstrate a requirement for the CD4 molecule in antibody-enhanced HIV-1 infection via FcR. Soluble CD4 prevented infection by HIV-1 antibody-treated virus, and enhancement of infection of virus-antibody complexes was abrogated by a monoclonal antibody to CD4 (anti-Leu3a antibody). Treatment of human macrophages with an anti-CD4 antibody also inhibited antibody-enhanced HIV-1 infection of macrophages, supporting our contention that antibody-dependent enhancement of HIV-1 infection via FcR requires CD4 interaction with the virus glycoprotein.
Takeda
A
A
Department of Medicine, University of Massachusetts Medical School, Worcester 01655.
Sweet
R W
RW
Ennis
F A
FA
D000911:Antibodies, Monoclonal; D000943:Antigens, Differentiation / Q000502:physiology*; D015704:CD4 Antigens / Q000502:physiology*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology / Q000382:microbiology*; D002460:Cell Line; D004705:Endocytosis; D006678:HIV / Q000254:growth & development*; D015483:HIV Antibodies / Q000276:immunology*; D015658:HIV Infections / Q000276:immunology*; D006801:Humans; D066298:In Vitro Techniques; D008264:Macrophages / Q000382:microbiology; D011961:Receptors, Fc / Q000502:physiology*; D017452:Receptors, IgG; D012995:Solubility
D000911:Antibodies, Monoclonal; D000943:Antigens, Differentiation; D015704:CD4 Antigens; D015483:HIV Antibodies; D011961:Receptors, Fc; D017452:Receptors, IgG