Journal
EMBO JOURNAL
Volume 39, Issue 11, Pages -Publisher
WILEY
DOI: 10.15252/embj.2019103285
Keywords
desuccinylation; innate immunity; MAVS; SIRT5; viral infection
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Funding
- National Key R & D Program of China [2018YFD0900602]
- National Natural Science Foundation of China [31830101, 31721005, 31671315, 31772872]
- Strategic Priority Research Program of the Chinese Academy of Sciences [XDA24010308]
- Youth Innovation Promotion Association (CAS)
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RLR-mediated type I IFN production plays a pivotal role in innate antiviral immune responses, where the signaling adaptor MAVS is a critical determinant. Here, we show that MAVS is a physiological substrate of SIRT5. Moreover, MAVS is succinylated upon viral challenge, and SIRT5 catalyzes desuccinylation of MAVS. Mass spectrometric analysis indicated that Lysine 7 of MAVS is succinylated. SIRT5-catalyzed desuccinylation of MAVS at Lysine 7 diminishes the formation of MAVS aggregation after viral infection, resulting in the inhibition of MAVS activation and leading to the impairment of type I IFN production and antiviral gene expression. However, the enzyme-deficient mutant of SIRT5 (SIRT5-H158Y) loses its suppressive role on MAVS activation. Furthermore, we show that Sirt5-deficient mice are resistant to viral infection. Our study reveals the critical role of SIRT5 in limiting RLR signaling through desuccinylating MAVS.
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