Details

Autor(en) / Beteiligte

• Yamashiro, Lívia H.
• Wilson, Stephen C.
• Morrison, Huntly M.
• Karalis, Vasiliki
• Chung, Jing-Yi J.
• Chen, Katherine J.
• Bateup, Helen S.
• Szpara, Moriah L.
• Lee, Angus Y.
• Cox, Jeffery S.
• Vance, Russell E.

Titel

Interferon-independent STING signaling promotes resistance to HSV-1 in vivo

Ist Teil von

• Nature communications, 2020-07, Vol.11 (1), p.3382-3382, Article 3382

Ort / Verlag

London: Nature Publishing Group UK

Erscheinungsjahr

2020

Quelle

MEDLINE

Beschreibungen/Notizen

• 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. STING is considered central to antiviral immunity via induction of type 1 interferons, but can also activate autophagy. Here the authors made two mice with different STING mutations that differentially affect these antiviral responses, and surprisingly show that inhibiting STING-dependent type 1 interferon production does not affect susceptibility to HSV-1 infection.