Immune-Specific Immunoglobulin G-Mediated Enhancement of Human Immunodeficiency Virus-Induced IFN-αProduction

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Abstract
Interferon-α (IFN-α) 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-α. Subsequently, preparations of pooled human immunoglobulin G (IgG) have also been shown to enhance poliovirus (PV)-induced IFN-α production. The current work establishes IgG as the serum mediator that enhances induction of IFN-α by HIV. Our studies also establish the ability of sera from individual subjects to enhance PV-induced IFN-α production. HIV-induced IFN-α production was enhanced maximally by >4000-fold and by an average of 25-fold. Sera from 74 people enhanced PV- induced IFN-α from undetectable levels to an average of 615 units (range 7-4679 units). The ability of individual sera to enhance IFN-α production by HIV and PV persisted undiminished in patients with AIDS. IgG-mediated enhancement of IFN-α 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-α 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.