Immune-specific immunoglobulin G-mediated enhancement of human immunodeficiency virus-induced IFN-alpha production

Interferon-alpha (IFN-alpha) is synthesized as an integral part of innate immunity to viral infection. We previously provided preliminary evidence that antibody-containing serum from HIV-infected individuals enhanced HIV-induced production of IFN-alpha. Subsequently, preparations of pooled human immunoglobulin G (IgG) have also been shown to enhance poliovirus (PV)-induced IFN-alpha production. The current work establishes IgG as the serum mediator that enhances induction of IFN-alpha by HIV. Our studies also establish the ability of sera from individual subjects to enhance PV-induced IFN-alpha production. HIV-induced IFN-alpha production was enhanced maximally by >4000-fold and by an average of 25-fold. Sera from 74 people enhanced PV- induced IFN-alpha from undetectable levels to an average of 615 units (range 7-4679 units). The ability of individual sera to enhance IFN-alpha production by HIV and PV persisted undiminished in patients with AIDS. IgG-mediated enhancement of IFN-alpha production was similar to that induced by IgG and PV and was blocked by IgG Fc fragments. Demonstration of the selective enhancement of HIV-induced IFN-alpha production by IgG from HIV-seropositive individuals provides further evidence for the existence of antigen-specific upregulation of a critical component of innate antiviral immunity by the adaptive Th2 immune response.