The Fc and not CD4 receptor mediates antibody enhancement of HIV infection in human cells.
Antibodies that enhance human immunodeficiency virus (HIV) infectivity have been found in the blood of infected individuals and in infected or immunized animals. These findings raise serious concern for the development of a safe vaccine against acquired immunodeficiency syndrome. To address the in vivo relevance and mechanism of this phenomenon, antibody-dependent enhancement of HIV infectivity in peripheral blood macrophages, lymphocytes, and human fibroblastoid cells was studied. Neither Leu3a, a monoclonal antibody directed against the CD4 receptor, nor soluble recombinant CD4 even at high concentrations prevented this enhancement. The addition of monoclonal antibody to the Fc receptor III (anti-FcRIII), but not of antibodies that react with FcRI or FcRII, inhibited HIV type 1 and HIV type 2 enhancement in peripheral blood macrophages. Although enhancement of HIV infection in CD4+ lymphocytes could not be blocked by anti-FcRIII, it was inhibited by the addition of human immunoglobulin G aggregates. The results indicate that the FcRIII receptor on human macrophages and possibly another Fc receptor on human CD4+ lymphocytes mediate antibody-dependent enhancement of HIV infectivity and that this phenomenon proceeds through a mechanism independent of the CD4 protein.
Homsy
J
J
Department of Medicine, School of Medicine, University of California, San Francisco 94143.
Meyer
M
M
Tateno
M
M
Clarkson
S
S
Levy
J A
JA
D000163:Acquired Immunodeficiency Syndrome / Q000276:immunology*; D000818:Animals; D000911:Antibodies, Monoclonal; D000920:Antibody-Dependent Cell Cytotoxicity; D006168:Guinea Pigs; D015483:HIV Antibodies / Q000096:biosynthesis / Q000276:immunology*; D015497:HIV-1 / Q000276:immunology*; D015498:HIV-2 / Q000276:immunology*; D006801:Humans; D066298:In Vitro Techniques; D002679:Pan troglodytes; D011961:Receptors, Fc / Q000502:physiology*; D015728:Receptors, HIV; D011991:Receptors, Virus / Q000502:physiology*
D000911:Antibodies, Monoclonal; D015483:HIV Antibodies; D011961:Receptors, Fc; D015728:Receptors, HIV; D011991:Receptors, Virus