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Nat Commun. 2016 Feb 19;7:10680. doi: 10.1038/ncomms10680.

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

Author information

1
Department of Biomedicine, Aarhus University, Aarhus 8000, Denmark.
2
Aarhus Research Center for Innate Immunity, Aarhus University, Aarhus 8000, Denmark.
3
Department of Molecular Biology and Genetics, Aarhus University, Aarhus 8000, Denmark.
4
Division of Infectious Diseases and Immunology, Department of Medicine, University of Massachusetts, Amherst, Massachusetts M01003, USA.
5
Psychiatric Department, Aarhus University Hospital, Aarhus 8000, Denmark.
6
Department of Immunology, School of Basic Medical Sciences, Fudan University, Shanghai 200433, China.
7
Department of Molecular and Cellular Biology, University of California, Berkeley, California 94720, USA.
8
Institute of Molecular Medicine, University Hospital, University of Bonn, 53127 Bonn, Germany.
9
Department of Medical Microbiology, University Medical Center, Utrecht 3508GA, The Netherlands.
10
Skauvaccines, Aarhus Nord 8200, Denmark.

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.

PMID:
26893169
PMCID:
PMC4762884
DOI:
10.1038/ncomms10680
[Indexed for MEDLINE]
Free PMC Article

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