Virus infection causes various types of diseases in humans, and the innate immune responses serve as the first line of defense against viruses. Virus infection causes rapid induction of antiviral and inflammatory genes in the infected cells, leading to the establishment of an antiviral state in the host. Virus infection is recognized by the pattern-recognition receptors, which activate the transcription factors IRF3 and NF-kB, to induce antiviral genes, e.g., interferons (IFNs). IFNs further amplify the response by inducing IFN-stimulated genes (ISGs), which specifically inhibit the steps of the viral life cycle. Recently we performed a high throughput screen to isolate novel ISGs against virus replication. Our screen revealed TDRD7, a novel ISG that inhibits virus-induced autophagy to suppress virus replication. It has become increasingly clear that in addition to viral load, virus-induced inflammation is a major determinant of viral pathogenesis. Our studies revealed that IRF3 inhibits viral inflammation by inhibiting NF-kB, the major transcription factor responsible for inflammatory gene induction. We used various cell types to show that IRF3 deficiency caused enhanced NF-kB activation and inflammatory responses. IRF3 deficiency causes susceptibility to viral diseases, and both ISG-inducing and anti-inflammatory functions contribute to the protection. Targeting these pathways may help reveal new therapeutics that can be applied to treat viral infection.
Audience take away:
- Audience will learn how innate immune response provides antiviral protection.
- The audience can use the knowledge to enrich their teaching and research.
- Novel therapeutics can be developed in the future.