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 Bahrami, Jakob Giehm Mikkelsen, Rune Hartmann and Søren R. Paludan ()
Additional contact information
Christian K. Holm: Aarhus University
Stine H. Rahbek: Aarhus University
Hans Henrik Gad: Aarhus Research Center for Innate Immunity, Aarhus University
Rasmus O. Bak: Aarhus University
Martin R. Jakobsen: Aarhus University
Zhaozaho Jiang: University of Massachusetts
Anne Louise Hansen: Aarhus University
Simon K. Jensen: Aarhus University
Chenglong Sun: Aarhus University
Martin K. Thomsen: Aarhus University
Anders Laustsen: Aarhus University
Camilla G. Nielsen: Aarhus University
Kasper Severinsen: Aarhus University Hospital
Yingluo Xiong: Aarhus University
Dara L. Burdette: University of California
Veit Hornung: Institute of Molecular Medicine, University Hospital, University of Bonn
Robert Jan Lebbink: University Medical Center
Mogens Duch: Aarhus University
Katherine A. Fitzgerald: University of Massachusetts
Shervin Bahrami: Aarhus University
Jakob Giehm Mikkelsen: Aarhus University
Rune Hartmann: Aarhus Research Center for Innate Immunity, Aarhus University
Søren R. Paludan: Aarhus University

Nature Communications, 2016, vol. 7, issue 1, 1-9

Abstract: 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.

Date: 2016
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DOI: 10.1038/ncomms10680

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