Recordon-Pinson, P. | bioRxiv Science

bioRxiv2025

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

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.

immunology↗

bioRxiv2021

SARS-CoV-2 transmission via apical syncytia release from primary bronchial epithelia and infectivity restriction in children epithelia

The beta-coronavirus SARS-CoV-2 is at the origin of a persistent worldwide pandemic. SARS-CoV-2 infections initiate in the bronchi of the upper respiratory tract and are able to disseminate to the lower respiratory tract eventually causing acute severe respiratory syndrome with a high degree of mortality in the elderly. Here we use reconstituted primary bronchial epithelia from adult and children donors to follow the infection dynamic following infection with SARS-CoV-2. We show that in bronchial epithelia derived from adult donors, infections initiate in multi-ciliated cells. Then, infection rapidly spread within 24-48h throughout the whole epithelia. Within 3-4 days, large apical syncytia form between multi-ciliated cells and basal cells, which dissipate into the apical lumen. We show that these syncytia are a significant source of the released infectious dose. In stark contrast to these findings, bronchial epithelia reconstituted from children donors are intrinsically more resistant to virus infection and show active restriction of virus spread. This restriction is paired with accelerated release of IFN compared to adult donors. Taken together our findings reveal apical syncytia formation as an underappreciated source of infectious virus for either local dissemination or release into the environment. Furthermore, we provide direct evidence that children bronchial epithelia are more resistant to infection with SARS-CoV-2 providing experimental support for epidemiological observations that SARS-CoV-2 cases fatality is linked to age. Significance StatementBronchial epithelia are the primary target for SARS-CoV-2 infections. Our work uses reconstituted bronchial epithelia from adults and children. We show that infection of adult epithelia with SARS-CoV-2 is rapid and results in the synchronized release of large clusters of infected cells and syncytia into the apical lumen contributing to the released infectious virus dose. Infection of children derived bronchial epithelia revealed an intrinsic resistance to infection and virus spread, probably as a result of a faster onset of interferon secretion. Thus, our data provide direct evidence for the epidemiological observation that children are less susceptible to SARS-CoV-2.

microbiology↗