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STAT3 Negatively Regulates Type I IFN-Mediated Antiviral Response
Journal of Immunology, 08/25/2011
Exclusive author commentary
Wang WB et al. – The results define STAT3 as a negative regulator of type I IFN response and provide a therapeutic target for viral infections.
Chien-Kuo Lee (08/28/2011) comments:
Type I interferon (IFN)s, including IFN-alpha and IFN-beta, have been the primary choice for the treatment of viral hepatitis,some cancers and multiple sclerosis. Although discovered more than 5 decades ago, the detailed mechanisms of type I IFNs in antiviral or anticancer remain to be determined. It has been known that type I IFNs activate STAT1, STAT2, and STAT3. While critical roles of STAT1 and STAT2 have been demonstrated in gene-targeted mice or in humans with mutations,the role of STAT3 in type I IFN response remains elusive. By using gain- and loss-of-function assays, we have demonstrated that STAT3 suppresses IFN-mediated antiviral responses. In addition, STAT3 also inhibits virus-triggered innate immunity. In sum, these results define STAT3 as a negative regulator of type I IFN response and provide a therapeutic target for viral infections.
