| First Author | Hu Z | Year | 2023 |
| Journal | Sci Adv | Volume | 9 |
| Issue | 25 | Pages | eadg2339 |
| PubMed ID | 37352355 | Mgi Jnum | J:338425 |
| Mgi Id | MGI:7495209 | Doi | 10.1126/sciadv.adg2339 |
| Citation | Hu Z, et al. (2023) VANGL2 inhibits antiviral IFN-I signaling by targeting TBK1 for autophagic degradation. Sci Adv 9(25):eadg2339 |
| abstractText | Stringent control of type I interferon (IFN-I) signaling is critical to potent innate immune responses against viral infection, yet the underlying molecular mechanisms are still elusive. Here, we found that Van Gogh-like 2 (VANGL2) acts as an IFN-inducible negative feedback regulator to suppress IFN-I signaling during vesicular stomatitis virus (VSV) infection. Mechanistically, VANGL2 interacted with TBK1 and promoted the selective autophagic degradation of TBK1 via K48-linked polyubiquitination at Lys(372) by the E3 ligase TRIP, which serves as a recognition signal for the cargo receptor OPTN. Furthermore, myeloid-specific deletion of VANGL2 in mice showed enhanced IFN-I production against VSV infection and improved survival. In general, these findings revealed a negative feedback loop of IFN-I signaling through the VANGL2-TRIP-TBK1-OPTN axis and highlighted the cross-talk between IFN-I and autophagy in preventing viral infection. VANGL2 could be a potential clinical therapeutic target for viral infectious diseases, including COVID-19. |
