Title: Tupaia OASL1 promotes cellular antiviral immune responses by recruiting MDA5 to MAVS.
Author: Yao YL, Yu D, Xu L, Gu T, Li Y, Zheng X, Bi R, Yao YG.
Publication Name:JOURNAL OF IMMUNOLOGY
Pub Year: 2020
Volume: 205
Issue:12
Page Number:3419-3428
Doi:10.4049/jimmunol.2000740
IF: 4.718
Abstract:
Melanoma differentiation-associated gene 5 (MDA5) is a key cytoplasmic dsRNA sensor. Upon bindingtoinvading viral RNA, activatedMDA5is recruitedtomitochondria and interacts with mitochondrialantiviralsignaling gene (MAVS)toinitiate innateantiviralimmuneresponses. The elegant regulation of this process remains elusive. In this study, using the Chinese tree shrew (Tupaiabelangeri chinensis), which is genetically closetoprimates, we identified theTupaiaoligoadenylate synthetases-like 1 (tOASL1) as a positive regulator of theTupaiaMDA5(tMDA5) andTupaiaMAV5 (tMAV5)-mediated IFN signaling. Over-expression of tOASL1 significantly potentiated the RNA virus-triggered induction of the type I IFNs and downstreamantiviralgenes. Conversely, knockdown of tOA5L1 had an impairedantiviralimmuneresponse. 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 mechanismbywhich tOA5L1 contributestohostantiviralresponsesvia enhancing tMDA5 and tMAV5 interaction.
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