RIG-I- AND TRIM25-MEDIATED IMMUNE RESPONSE AND EVASION OF INFLUENZA A VIRUS

Harvard Medical School, Boston MA

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Abstract

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. Primary support for the subproject and the subproject's principal investigator may have been provided by other sources, including other NIH sources. The Total Cost listed for the subproject likely represents the estimated amount of Center infrastructure utilized by the subproject, not direct funding provided by the NCRR grant to the subproject or subproject staff. The interconnection between the cytosolic viral RNA receptor RIG-I and the TRIM protein family member, TRIM25, represents a novel regulatory pathway that is important for the induction of interferon (IFN)-mediated host innate immunity against various RNA viruses, including influenza A viruses. To antagonize the host antiviral IFN response, viruses have evolved numerous sophisticated mechanisms. Our previous work demonstrated that the NS1 protein of human, avian and swine influenza A viruses interacts with and inhibits TRIM25 ubiquitin E3 ligase, thereby potently suppressing RIG-I ubiquitination and signal transducing activity. Thus, our goal here is to delineate the detailed mechanisms by which influenza A virus NS1 inhibits the RIG-I- and TRIM25-triggered IFN response. In addition, this study attempts to unveil the biological role of TRIM25 in the host antiviral response against influenza virus infection.