| First Author | Huai W | Year | 2016 |
| Journal | Proc Natl Acad Sci U S A | Volume | 113 |
| Issue | 42 | Pages | 11925-11930 |
| PubMed ID | 27698125 | Mgi Jnum | J:238492 |
| Mgi Id | MGI:5822940 | Doi | 10.1073/pnas.1601556113 |
| Citation | Huai W, et al. (2016) Mint3 potentiates TLR3/4- and RIG-I-induced IFN-beta expression and antiviral immune responses. Proc Natl Acad Sci U S A 113(42):11925-11930 |
| abstractText | Type I IFNs (IFN-alpha/beta) play crucial roles in the elimination of invading viruses. Multiple immune cells including macrophages recognize viral infection through a variety of pattern recognition receptors, such as Toll-like receptors (TLRs) and retinoic acid-inducible gene-I (RIG-I)-like receptors, and initiate type I IFN secretion and subsequent antiviral immune responses. However, the mechanisms by which host immune cells can produce adequate amounts of type I IFNs and then eliminate viruses effectively remain to be further elucidated. In the present study, we show that munc18-1-interacting protein 3 (Mint3) expression can be markedly induced during viral infection in macrophages. Mint3 enhances TLR3/4- and RIG-I-induced IRF3 activation and IFN-beta production by promoting K63-linked polyubiquitination of TNF receptor-associated factor 3 (TRAF3). Consistently, Mint3 deficiency greatly attenuated antiviral immune responses and increased viral replication. Therefore, we have identified Mint3 as a physiological positive regulator of TLR3/4 and RIG-I-induced IFN-beta production and have outlined a feedback mechanism for the control of antiviral immune responses. |
