Human type-I interferon omega holds potent antiviral properties and promotes cytolytic CD8+ T cell responses

Abstract

The type-I interferon family is well known for its critical role in innate immunity. It comprises several members, among which IFN-2 and IFN-{beta} are the most extensively studied, with important antiviral and immune-modulatory functions. Recent findings linking autoantibodies against type-I interferons to severe COVID-19 suggest a potential role for IFN-{omega} in combating SARS-CoV-2 infection. However, little is known about human IFN-{omega}, as most research on this interferon has been conducted in feline models. Here, we demonstrate that human IFN-{omega} is secreted at levels comparable to those of IFN-2 or IFN-{beta} upon stimulation with inflammatory agonists and triggers a robust antiviral response, inhibiting SARS-CoV-2 infection in vitro. Moreover, IFN-{omega} enhances the effector functions of antigen-specific CD8+ T cells primed de novo from healthy donor cells, highlighting its capacity to promote strong cellular immunity. Our results position IFN-{omega} as a key member of the type-I interferon family, with promising potential for therapeutic and vaccine applications. Author SummaryType-I interferons are pleiotropic cytokines, including IFN- and IFN-{beta}, which are well known for their antiviral activities. Here, we report on the functional characteristics of human IFN-{omega}, a neglected member of the type-I IFN family, which has primarily been studied in feline models. We show here that human IFN-{omega} induces intense downstream signaling in cells resulting in the upregulation of antiviral genes, and efficient restriction of SARS-CoV-2 replication. IFN-{omega} also promotes the acquisition of strong cytolytic functions by antigen primed CD8+ T cells. Overall, our findings portray human IFN-{omega} as a major antiviral molecule, similar to the well-studied and highly effective IFN-2. The secretion of IFN-{omega} upon infection is likely to be crucial for effective control of multiple viruses, advocating for its use in therapeutic approaches in humans.