@article{482c92d8d1714fcaadc30e4bda996fbd,
title = "Interferon-independent STING signaling promotes resistance to HSV-1 in vivo",
abstract = "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.",
author = "Yamashiro, {L{\'i}via H.} and Wilson, {Stephen C.} and Morrison, {Huntly M.} and Vasiliki Karalis and Chung, {Jing Yi J.} and Chen, {Katherine J.} and Bateup, {Helen S.} and Szpara, {Moriah L.} and Lee, {Angus Y.} and Cox, {Jeffery S.} and Vance, {Russell E.}",
note = "Funding Information: We thank members of the R.E.V., Barton, Stanley, and Cox labs for discussions, Laura Flores, Peter Dietzen, and Roberto Chavez for technical assistance, Hector Nolla and Alma Valeros and the Cancer Research Laboratory for flow cytometry. We thank Dr. Mary West and Dr. Pingping He of the High-Throughput Screening Facility (HTSF) at UC Berkeley. This work was performed in part in the HTSF, which provided the Perkin Elmer Opera Phenix, funded by NIH Instrument Grant S10OD021828 with the assistance of Christopher Noel. We thank the CNR Biological Imaging Facility at UC Berkeley for the Carl Zeiss LSM710 confocal microscope, funded by NIH S10 program 1S10RR026866-01 with the assistance of Steven Ruzin and Denise Schichnes. We thank Chris Bowen and Daniel Renner in the Szpara lab for assistance with viral genome sequencing and analysis. R.E.V. was supported by an investigator in the Pathogenesis of Infectious Diseases awards from the Burroughs Wellcome Fund. R.E.V. is an HHMI Investigator and is supported by NIH grants AI075039 and AI066302.",
year = "2020",
month = dec,
day = "1",
doi = "10.1038/s41467-020-17156-x",
language = "English (US)",
volume = "11",
journal = "Nature Communications",
issn = "2041-1723",
publisher = "Nature Publishing Group",
number = "1",
}