The Fc and not CD4 Receptor Mediates Antibody Enhancement of HIV Infection in Human Cells

Abstract

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.

CD95 (Fas) Ligand-Expressing Vesicles Display Antibody-Mediated, FcR-Dependent Enhancement of Cytotoxicity

“…Finally, our demonstration that the IgG anti-FasL mAb can focus FasL VP onto target cells through Fc/FcR interactions is reminiscent of several earlier studies of viral replication in FcR ϩ cells (27)(28)(29) (28). It is also known that neutralized Dengue virus displays residual infectivity mediated through high-affinity IgG FcR (29).…”

Neutralization sensitivity and accessibility of continuous B cell epitopes of the feline immunodeficiency virus envelope

“…In fact, several monospecific sera augmented infection of FIV by two-or threefold (Table 4). The enhancement of virus infection in the presence of antibodies specific for envelope glycoproteins has previously been observed for FIV Lombardi et al, 1994;Siebelink et al, 1995b) as well as for numerous other viruses including HIV (reviewed in Mascola et al, 1993) and several mechanisms have been proposed (Robinson et al, 1990;Takeda et al, 1988;Homsy et al, 1989). It is noteworthy that we did not observe this phenomenon in CrFK fibroblasts, which may lack functional Fc receptors or other molecules required for antibody-mediated enhancement of infection.…”

Macrophages and HIV-1: dangerous liaisons

“…Moreover, since the very beginning of the AIDS pandemic it has been known that the levels of circulating immune complexes (including HIV-specific CIC) are elevated in HIV-positive patients, independent of other infections (Carini et al, 1987;Tausk et al, 1986). HIV-1 immune complexes may, however, facilitate HIV-1 entry through FcRs or complement receptors (Homsy, 1989;Takeda et al, 1990). Thus, the stimulation of monocytes and resident macrophages by immune complexes through FcR might modulate HIV-1 infection and spread in opposite directions.…”