2025/02/14 by Hoang Oanh Nguyen, Patrícia Recordon-Pinson, Marie‐Line Andréola +2 · 1 voice
Medicine · Immunology and Microbiology · Agricultural and Biological Sciences · #SARS-CoV-2 and COVID-19 Research #interferon and immune responses #Animal Virus Infections Studies
paper · doi:10.1101/2025.02.13.638030
openalex publication_date 2025/02/14 · openalex created_date 2025/02/15 · openalex updated_date 2026/07/22
Abstract The type-I interferon family is well known for its critical role in innate immunity. It comprises several members, among which IFN-α2 and IFN-β 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-ω in combating SARS-CoV-2 infection. However, little is known about human IFN-ω, as most research on this interferon has been conducted in feline models. Here, we demonstrate that human IFN-ω is secreted at levels comparable to those of IFN-α2 or IFN-β upon stimulation with inflammatory agonists and triggers a robust antiviral response, inhibiting SARS-CoV-2 infection in vitro . Moreover, IFN-ω 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-ω as a key member of the type-I interferon family, with promising potential for therapeutic and vaccine applications. Author Summary Type-I interferons are pleiotropic cytokines, including IFN-α and IFN-β, which are well known for their antiviral activities. Here, we report on the functional characteristics of human IFN-ω, a neglected member of the type-I IFN family, which has primarily been studied in feline models. We show here that human IFN-ω induces intense downstream signaling in cells resulting in the upregulation of antiviral genes, and efficient restriction of SARS-CoV-2 replication. IFN-ω also promotes the acquisition of strong cytolytic functions by antigen primed CD8 + T cells. Overall, our findings portray human IFN-ω as a major antiviral molecule, similar to the well-studied and highly effective IFN-α 2 . The secretion of IFN-ω upon infection is likely to be crucial for effective control of multiple viruses, advocating for its use in therapeutic approaches in humans.