Tupaia OASL1 Promotes Cellular Antiviral Immune Responses by Recruiting MDA5 to MAVS,The Journal of Immunology

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Tupaia OASL1 Promotes Cellular Antiviral Immune Responses by Recruiting MDA5 to MAVS
The Journal of Immunology ( IF 4.4 ) Pub Date : 2020-11-13 , DOI: 10.4049/jimmunol.2000740
Yu-Lin Yao _{1,

2,

3} , Dandan Yu _{1,

2,

3} , Ling Xu _{1,

2} , Tianle Gu _{1,

2,

3} , Yu Li _{1,

2,

3} , Xiao Zheng _{1,

2,

4} , Rui Bi _{1,

2,

3} , Yong-Gang Yao _{1,

2,

3,

5,

6}

Affiliation

Key Points Tupaia OASL1 is critical for RNA virus–induced antiviral signaling transduction. tOASL1 is associated with mitochondria. tOASL1 is a positive regulator of type I IFN induction by recruiting tMDA5 to tMAVS. Visual Abstract 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 MAVS (tMAVS)–mediated IFN signaling. Overexpression of tOASL1 significantly potentiated the RNA virus-triggered induction of the type I IFNs and downstream antiviral genes. Conversely, knockdown of tOASL1 had an impaired antiviral immune response. Mechanistically, tOASL1 was associated with mitochondria and directly interacted with tMDA5 and tMAVS. Upon RNA virus infection, tOASL1 enhanced the interaction between tMDA5 and tMAVS via its OAS and UBL domains. Our results revealed a novel mechanism by which tOASL1 contributes to host antiviral responses via enhancing tMDA5 and tMAVS interaction.

更新日期：2020-11-13

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