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

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

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Humans
  • Influenza A virus / genetics
  • Influenza A virus / physiology*
  • Influenza, Human / enzymology*
  • Influenza, Human / genetics
  • Influenza, Human / metabolism
  • Influenza, Human / virology
  • Interferon Type I / genetics
  • Interferon Type I / metabolism
  • Membrane Proteins / genetics
  • Membrane Proteins / metabolism*
  • Mice
  • Nucleotidyltransferases / genetics
  • Nucleotidyltransferases / metabolism*
  • RNA Virus Infections / enzymology*
  • RNA Virus Infections / genetics
  • RNA Virus Infections / metabolism
  • RNA Virus Infections / virology
  • RNA Viruses / genetics
  • RNA Viruses / physiology

Substances

  • Interferon Type I
  • MPYS protein, mouse
  • Membrane Proteins
  • STING protein, human
  • MB21D1 protein, human
  • Nucleotidyltransferases
  • cGAS protein, mouse