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 early detection of invading viruses by the host depends on a limited number of intracellular receptors that sense conserved structural components of viruses and subsequently initiate signaling cascades leading to type-I-interferon (IFN) induction. Retinoic acid-inducible gene I (RIG-I) has emerged as a key cytosolic receptor for sensing RNA viruses, including influenza virus and hepatitis C virus. The main goal of this study is to investigate how the host innate immune system recognizes virus infection and triggers IFN responses, with a specific focus on the RIG-I protein and the regulation of its activity. Our previous studies demonstrated that the viral RNA sensor RIG-I and the RING ubiquitin E3 ligase TRIM25 play key roles in the IFN response against RNA virus infection. Despite the wealth of knowledge resulting from recent discoveries of molecular components in the RIG-I/TRIM25 signaling pathway, the regulation of their antiviral activities has not been well studied;but it is exactly the regulation of the IFN production, which dictates the outcome of the viral infection and pathogenesis. Thus, this study is dedicated to identify RIG-I posttranslational modifications, and to investigate how posttranslational modifications affect the RIG-I activity to limit viral replication. Furthermore, this study aims at identifying host factors with a pivotal role in the regulation of RIG-I signaling pathway, as well as elucidating their roles for RIG-I host surveillance against RNA virus infections.
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