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Influenza A virus NS1 targets the ubiquitin ligase TRIM25 to evade recognition by the host viral RNA sensor RIG-I.
| Content Provider | Semantic Scholar |
|---|---|
| Author | Gack, Michaela U. Albrecht, Randy A. Urano, Tomohiko Inn, Kyung-Soo Huang, I-Chueh Carnero, Elena Farzan, Michael Inoue, Satoshi Jung, Jae U. García-Sastre, Adolfo |
| Copyright Year | 2009 |
| Abstract | The ubiquitin ligase TRIM25 mediates Lysine 63-linked ubiquitination of the N-terminal CARD domains of the viral RNA sensor RIG-I to facilitate type I interferon (IFN) production and antiviral immunity. Here, we report that the influenza A virus nonstructural protein 1 (NS1) specifically inhibits TRIM25-mediated RIG-I CARD ubiquitination, thereby suppressing RIG-I signal transduction. A novel domain in NS1 comprising E96/E97 residues mediates its interaction with the coiled-coil domain of TRIM25, thus blocking TRIM25 multimerization and RIG-I CARD domain ubiquitination. Furthermore, a recombinant influenza A virus expressing an E96A/E97A NS1 mutant is defective in blocking TRIM25-mediated antiviral IFN response and loses virulence in mice. Our findings reveal a mechanism by which influenza virus inhibits host IFN response and also emphasize the vital role of TRIM25 in modulating antiviral defenses. |
| File Format | PDF HTM / HTML |
| DOI | 10.1016/j.chom.2009.04.006 |
| PubMed reference number | 19454348 |
| Journal | Medline |
| Volume Number | 5 |
| Issue Number | 5 |
| Alternate Webpage(s) | http://education.sdsc.edu/teachertech/downloads/abstract2.pdf |
| Alternate Webpage(s) | https://doi.org/10.1016/j.chom.2009.04.006 |
| Journal | Cell host & microbe |
| Language | English |
| Access Restriction | Open |
| Content Type | Text |
| Resource Type | Article |
