Seminaire CIRI: Pr. Ping WANG

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Date / Heure
Date(s) - 13/11/2018
11 h 00 min - 12 h 00 min

Amphi Pasteur, Tour CERVI

Pr. Ping WANG ( School of Medicine, Tongji University, Shanghai, China), “ Regulation of Cytosolic DNA induced type I Interferon production by deubiquitination

DNA viral infection activates danger signals that are transmitted via DNA sensor-STING signaling cascades. Stimulator of IFN genes (STING) is a central adaptor protein that mediates the innate immune responses to DNA virus infection. Although ubiquitination is essential for STING function, how the Ubiquitination/deubiquitination system is regulated by virus infection to control STING activity remains unknown. We found that USP21 is an important deubiquitinating enzyme for STING and that it negatively regulates the DNA virus-induced production of type I interferons by hydrolyzing K27/63-linked polyubiquitin chain on STING. HSV-1 infection recruited USP21 to STING at late stage by p38-mediated phosphorylation of USP21 at Ser538. Inhibition of p38 MAPK enhanced the production of IFNs in response to virus infection and protected mice from lethal HSV-1 infection. Thus, our study reveals a critical role of p38-mediated USP21 phosphorylation in regulating STING-mediated antiviral functions and identifies p38- USP21 axis as an important pathway that DNA virus adopts to avoid innate immunity responses.

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