Defining the role of TRIM proteins in vector-borne bunyavirus infection

Project Summary/Abstract Bunyaviruses are a large group of RNA viruses that can cause severe disease in humans worldwide. Currently, there are no specific antiviral treatments for any bunyaviruses. As the first line of defense against invading viral pathogens, host innate immune system plays an important role in sensing viral infection and inducing type I interferons (IFNs) and interferon-stimulated genes (ISGs). Many ISGs have antiviral activities and block viral infection at different steps in the virus life cycle. IFN response plays a critical role in the control of bunyaviral infection. However, the mechanisms by which host innate immune system restrict bunyavirus infection are poorly understood. Tripartite motif (TRIM) proteins are a family of more than 70 members in human that play important roles in the antiviral immunity by either regulating innate immune sensing pathways or directly suppressing viral infection as antiviral ISGs. However, only a small portion of these proteins have been characterized functionally and the contribution of TRIM proteins to the host defense against bunyaviruses remains to be elucidated. We hypothesize that TRIM proteins play regulatory roles in the control of host innate immune response against bunyaviruses. Therefore, using Rift Valley fever virus (RVFV) and La Crosse virus (LACV) as examples, this proposal will characterize the role of TRIM proteins in the host innate antiviral immunity to vector-borne bunyavirus infection. To achieve these goals, our specific aims will (1) characterize the TRIM proteins that regulate bunyavirus infection and (2) define the antiviral action and the molecular determinants of one antiviral TRIM protein we have identified. The results from these studies will advance our understanding of virus-host interactions and could provide valuable information for the development of novel antiviral therapeutics.