Induction of USP25 by Viral Infection Promotes Innate Antiviral Responses by Mediating the Stabilization of TRAF3 and TRAF6

Overview

Journal Proc Natl Acad Sci U S A

Specialty Science

Date 2015 Aug 26

PMID 26305951

Citations 68

Authors

Dandan Lin

Man Zhang

Meng-Xin Zhang

Yujie Ren

Jie Jin

Quanyi Zhao

Zishu Pan

Min Wu

Hong-Bing Shu

Chen Dong

Bo Zhong

Affiliations

Soon will be listed here.

Abstract

Host pathogen-recognition receptors detect nucleic acid from invading viruses and initiate a series of signaling pathways that lead to the production of type I interferons (IFNs) and proinflammatory cytokines. Here, we found that a viral infection-induced deubiquitinase (DUB), ubiquitin-specific protease 25 (USP25) was required for host defense against RNA and DNA viruses. The activation of transcription factors IRF3 and NF-κB was impaired and the production of type I IFNs and proinflammatory cytokines was inhibited in Usp25-/- cells compared with the wild-type counterparts after RNA or DNA viruses infection. Consistently, USP25 deficient mice were more susceptible to H5N1 or HSV-1 infection compared with the wild-type mice. USP25 was associated with TRAF3 and TRAF6 after infection by RNA or DNA viruses and protected virus-induced proteasome-dependent or independent degradation of TRAF3 and TRAF6, respectively. Moreover, reconstitution of TRAF3 and TRAF6 into Usp25-/- MEFs restored virus-triggered production of type I IFNs and proinflammatory cytokines. Our findings thus reveal a previously uncovered positive feedback regulation of innate immune responses against RNA and DNA viruses by USP25.

Citing Articles

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