Tupaia Oasl1 Promotes Cellular Antiviral Immune Responses By Recruiting Mda5 To Mavs

Melanoma differentiation-associated gene 5 (MDA5) is a key cytoplasmic dsRNA sensor. Upon binding to invading viral RNA, activated MDA5 is recruited to mitochondria and interacts with mitochondrial antiviral signaling gene (MAVS) to initiate innate antiviral immune responses. The elegant regulation of this process remains elusive. In this study, using the Chinese tree shrew (Tupaia belangeri chinensis), which is genetically close to primates, we identified the Tupaia oligoadenylate synthetases-like 1 (tOASL1) as a positive regulator of the Tupaia MDA5 (tMDA5) and Tupaia MAV5 (tMAV5)-mediated IFN signaling. Over-expression of tOASL1 significantly potentiated the RNA virus-triggered induction of the type I IFNs and downstream antiviral genes. Conversely, knockdown of tOA5L1 had an impaired antiviral immune response. Mechanistically, tOA5L1 was associated with mitochondria and directly interacted with tMDA5 and tMAV5. Upon RNA virus infection, tOA5L1 enhanced the interaction between tMDA5 and tMAV5 via its OAS and UBL domains Our results revealed a novel mechanism by which tOA5L1 contributes to host antiviral responses via enhancing tMDA5 and tMAV5 interaction.