| First Author | Yamashiro LH | Year | 2020 |
| Journal | Nat Commun | Volume | 11 |
| Issue | 1 | Pages | 3382 |
| PubMed ID | 32636381 | Mgi Jnum | J:292197 |
| Mgi Id | MGI:6447560 | Doi | 10.1038/s41467-020-17156-x |
| Citation | Yamashiro LH, et al. (2020) Interferon-independent STING signaling promotes resistance to HSV-1 in vivo. Nat Commun 11(1):3382 |
| abstractText | The Stimulator of Interferon Genes (STING) pathway initiates potent immune responses upon recognition of DNA. To initiate signaling, serine 365 (S365) in the C-terminal tail (CTT) of STING is phosphorylated, leading to induction of type I interferons (IFNs). Additionally, evolutionary conserved responses such as autophagy also occur downstream of STING, but their relative importance during in vivo infections remains unclear. Here we report that mice harboring a serine 365-to-alanine (S365A) mutation in STING are unexpectedly resistant to Herpes Simplex Virus (HSV)-1, despite lacking STING-induced type I IFN responses. By contrast, resistance to HSV-1 is abolished in mice lacking the STING CTT, suggesting that the STING CTT initiates protective responses against HSV-1, independently of type I IFNs. Interestingly, we find that STING-induced autophagy is a CTT- and TBK1-dependent but IRF3-independent process that is conserved in the STING S365A mice. Thus, interferon-independent functions of STING mediate STING-dependent antiviral responses in vivo. |
