| First Author | Lin D | Year | 2015 |
| Journal | Proc Natl Acad Sci U S A | Volume | 112 |
| Issue | 36 | Pages | 11324-9 |
| PubMed ID | 26305951 | Mgi Jnum | J:226812 |
| Mgi Id | MGI:5698596 | Doi | 10.1073/pnas.1509968112 |
| Citation | Lin D, et al. (2015) Induction of USP25 by viral infection promotes innate antiviral responses by mediating the stabilization of TRAF3 and TRAF6. Proc Natl Acad Sci U S A 112(36):11324-9 |
| abstractText | 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-kappaB 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. |
