Loss-of-function mutations and suppression of innate antiviral proteins, such as OAS2 and OASL are associated with high viral infection rates in mice and humans. Because of their induction by interferons, these antiviral proteins are often referred to as interferon-stimulated genes (ISG). While recombinant interferon stimulates production of these antiviral proteins, type I interferon?s severe toxicity is the major limitation in its therapeutic utility. Additionally, pharmacological antivirals, such as acyclovir, have a high risk for triggering neutropenia and nephrotoxicity in vulnerable patient populations. Therefore, there is a significant unmet clinical need for new antiviral therapeutics. This need can be addressed by developing a full understanding of interferon-independent regulation of endogenous antiviral proteins and identifying targets for therapy and prevention by activation of this incredibly potent natural antiviral pathway. Our proposed work will answer important question: 1) Which interferon-independent signals and pathways can induce antiviral competence? 2) Does epithelial antiviral innate immunity differ on a single cell level? 3) What factors collaborate in the induction of innate antiviral immunity?
Skin constitutes a primary barrier to viral pathogens. Identifying interferon-independent innate immunity factors controlling antiviral responses is pivotal because such mechanisms adapt and respond much more rapidly than adaptive immune responses to environmental cues, like barrier disruption and virus infections. Enhancing innate antiviral immunity may change the way we treat and prevent viral infections and would benefit multiple patient populations at high risk for viral infections, including neonates, elderly, paraplegic patients, surgical patients, and patients suffering from atopic eczema.
