Zebrafish otud6b Negatively Regulates Antiviral Responses by Suppressing K63-Linked Ubiquitination of irf3 and irf7.
J Immunol
; 207(1): 244-256, 2021 07 01.
Article
in En
| MEDLINE
| ID: mdl-34183367
ABSTRACT
Ovarian tumor domain-containing 6B (OTUD6B) belongs to the OTU deubiquitylating enzyme family. In this study, we report that zebrafish otud6b is induced upon viral infection, and overexpression of otud6b suppresses cellular antiviral response. Disruption of otud6b 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 otud6b to repress IFN-1 activation and K63-linked polyubiquitination of irf3 and irf7. Moreover, otud6b 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 otud6b function and sheds new lights on the regulation of irf3 and irf7 by deubiquitination in IFN-1 signaling.
Full text:
1
Database:
MEDLINE
Main subject:
Viremia
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Carps
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Zebrafish Proteins
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Interferon Regulatory Factors
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Interferon Regulatory Factor-3
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Lysine
Limits:
Animals
Language:
En
Journal:
J Immunol
Year:
2021
Type:
Article