| First Author | Zhang Y | Year | 2020 |
| Journal | Nat Commun | Volume | 11 |
| Issue | 1 | Pages | 6000 |
| PubMed ID | 33243993 | Mgi Jnum | J:299848 |
| Mgi Id | MGI:6490735 | Doi | 10.1038/s41467-020-19849-9 |
| Citation | Zhang Y, et al. (2020) beta-arrestin 2 as an activator of cGAS-STING signaling and target of viral immune evasion. Nat Commun 11(1):6000 |
| abstractText | Virus infection may induce excessive interferon (IFN) responses that can lead to host tissue injury or even death. beta-arrestin 2 regulates multiple cellular events through the G protein-coupled receptor (GPCR) signaling pathways. Here we demonstrate that beta-arrestin 2 also promotes virus-induced production of IFN-beta and clearance of viruses in macrophages. beta-arrestin 2 interacts with cyclic GMP-AMP synthase (cGAS) and increases the binding of dsDNA to cGAS to enhance cyclic GMP-AMP (cGAMP) production and the downstream stimulator of interferon genes (STING) and innate immune responses. Mechanistically, deacetylation of beta-arrestin 2 at Lys171 facilitates the activation of the cGAS-STING signaling and the production of IFN-beta. In vitro, viral infection induces the degradation of beta-arrestin 2 to facilitate immune evasion, while a beta-blocker, carvedilol, rescues beta-arrestin 2 expression to maintain the antiviral immune response. Our results thus identify a viral immune-evasion pathway via the degradation of beta-arrestin 2, and also hint that carvedilol, approved for treating heart failure, can potentially be repurposed as an antiviral drug candidate. |
