Zebrafish otud6b Negatively Regulates Antiviral Responses by Suppressing K63-Linked Ubiquitination of irf3 and irf7

Ovarian tumor domain-containing 6B ( ) belongs to the OTU deubiquitylating enzyme family. In this study, we report that zebrafish is induced upon viral infection, and overexpression of suppresses cellular antiviral response. Disruption of in zebrafish increases the survival rate upon spring viremia of carp virus and grass carp reovirus exposure. Further assays indicate that otud6b interacts with irf3 and irf7 and diminishes traf6-mediated K63-linked polyubiquitination of irf3 and irf7. In addition, the OTU domain is required for to repress IFN-1 activation and K63-linked polyubiquitination of irf3 and irf7. Moreover, also attenuates tbk1 to bind to irf3 and irf7, resulting in the impairment of irf3 and irf7 phosphorylation. This study provides, to our knowledge, novel insights into function and sheds new lights on the regulation of and by deubiquitination in IFN-1 signaling.