Influenza A virus targets a cGAS-independent STING pathway that controls enveloped RNA viruses

Christian K. Holm, Stine H. Rahbek, Hans Henrik Gad, Rasmus O. Bak, Martin R. Jakobsen, Zhaozaho Jiang, Anne Louise Hansen, Simon K. Jensen, Chenglong Sun, Martin K. Thomsen, Anders Laustsen, Camilla G. Nielsen, Kasper Severinsen, Yingluo Xiong, Dara L. Burdette, Veit Hornung, Robert Jan Lebbink, Mogens Duch, Katherine A. Fitzgerald, Shervin BahramiJakob Giehm Mikkelsen, Rune Hartmann, Søren R. Paludan

Research output: Contribution to journalArticlepeer-review

120 Scopus citations

Abstract

Stimulator of interferon genes (STING) is known be involved in control of DNA viruses but has an unexplored role in control of RNA viruses. During infection with DNA viruses STING is activated downstream of cGAMP synthase (cGAS) to induce type I interferon. Here we identify a STING-dependent, cGAS-independent pathway important for full interferon production and antiviral control of enveloped RNA viruses, including influenza A virus (IAV). Further, IAV interacts with STING through its conserved hemagglutinin fusion peptide (FP). Interestingly, FP antagonizes interferon production induced by membrane fusion or IAV but not by cGAMP or DNA. Similar to the enveloped RNA viruses, membrane fusion stimulates interferon production in a STING-dependent but cGAS-independent manner. Abolishment of this pathway led to reduced interferon production and impaired control of enveloped RNA viruses. Thus, enveloped RNA viruses stimulate a cGAS-independent STING pathway, which is targeted by IAV.

Original languageEnglish (US)
Article number10680
JournalNature communications
Volume7
DOIs
StatePublished - Feb 19 2016
Externally publishedYes

ASJC Scopus subject areas

  • Chemistry(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Physics and Astronomy(all)

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