@article{5db8ccbbcc0045aba52866fb922ae2aa,
title = "Interferon-Independent Activities of Mammalian STING Mediate Antiviral Response and Tumor Immune Evasion",
abstract = "Type I interferon (IFN) response is commonly recognized as the main signaling activity of STING. Here, we generate the Sting1S365A/S365A mutant mouse that precisely ablates IFN-dependent activities while preserving IFN-independent activities of STING. StingS365A/S365A mice protect against HSV-1 infection, despite lacking the STING-mediated IFN response. This challenges the prevailing view and suggests that STING controls HSV-1 infection through IFN-independent activities. Transcriptomic analysis reveals widespread IFN-independent activities of STING in macrophages and T cells, and STING activities in T cells are predominantly IFN independent. In mouse tumor models, T cells in the tumor experience substantial cell death that is in part mediated by IFN-independent activities of STING. We found that the tumor induces STING-mediated cell death in T cells to evade immune control. Our data demonstrate that mammalian STING possesses widespread IFN-independent activities that are important for restricting HSV-1 infection, tumor immune evasion and likely also adaptive immunity.",
keywords = "HSV-1, IFN, STING, T cells, antiviral response, cancer immunology",
author = "Jianjun Wu and Nicole Dobbs and Kun Yang and Nan Yan",
note = "Funding Information: We thank Glen Barber (University of Miami) for the Sting1 −/− mice; David Leib (Dartmouth University) for the WT HSV-1 (strain 17); Bernard Moss (National Institutes of Health [NIH]) for the VACV (B5R-GFP); Ryan Huang, Robert Maples, and Gustavo Torres-Ramirez for mouse breeding; and the members of the Yan lab for helpful discussions. This work was supported by the National Institutes of Health ( AR067135 , AI134877 and AI151708 to N.Y.), the Cancer Prevention and Research Institute of Texas (CPRIT; RP180288 ), and the Burroughs Wellcome Fund (to N.Y.). Funding Information: We thank Glen Barber (University of Miami) for the Sting1?/? mice; David Leib (Dartmouth University) for the WT HSV-1 (strain 17); Bernard Moss (National Institutes of Health [NIH]) for the VACV (B5R-GFP); Ryan Huang, Robert Maples, and Gustavo Torres-Ramirez for mouse breeding; and the members of the Yan lab for helpful discussions. This work was supported by the National Institutes of Health (AR067135, AI134877 and AI151708 to N.Y.), the Cancer Prevention and Research Institute of Texas (CPRIT; RP180288), and the Burroughs Wellcome Fund (to N.Y.). J.W. performed most of the experiments. N.D. helped with the tumor and cytokine analysis. K.Y. helped with the initial generation of the Sting1S365A/S365A mice. J.W. and N.Y. wrote the paper with input from all of the coauthors. The authors declare no competing interests. Publisher Copyright: {\textcopyright} 2020 Elsevier Inc.",
year = "2020",
month = jul,
day = "14",
doi = "10.1016/j.immuni.2020.06.009",
language = "English (US)",
volume = "53",
pages = "115--126.e5",
journal = "Immunity",
issn = "1074-7613",
publisher = "Cell Press",
number = "1",
}