title: Influenza C virus NS1 protein counteracts RIG-I-mediated IFN signalling.
abstract: The nonstructural proteins 1 (NS1) from influenza A and B viruses are known as the main viral factors antagonising the cellular interferon (IFN) response, inter alia by inhibiting the retinoic acid-inducible gene I (RIG-I) signalling. The cytosolic pattern-recognition receptor RIG-I senses double-stranded RNA and 5'-triphosphate RNA produced during RNA virus infections. Binding to these ligands activates RIG-I and in turn the IFN signalling. We now report that the influenza C virus NS1 protein also inhibits the RIG-I-mediated IFN signalling. Employing luciferase-reporter assays, we show that expression of NS1-C proteins of virus strains C/JJ/50 and C/JHB/1/66 considerably reduced the IFN-β promoter activity. Mapping of the regions from NS1-C of both strains involved in IFN-β promoter inhibition showed that the N-terminal 49 amino acids are dispensable, while the C-terminus is required for proper modulation of the IFN response. When a mutant RIG-I, which is constitutively active without ligand binding, was employed, NS1-C still inhibited the downstream signalling, indicating that IFN inhibitory properties of NS1-C are not necessarily linked to an RNA binding mechanism.
authors.affiliation: Department of Molecular Biology, University of Salzburg, Billrothstrasse 11, 5020 Salzburg, Austria.
authors.forename: Karin
authors.initials: K
authors.lastname: Pachler
authors.forename: Reinhard
authors.initials: R
authors.lastname: Vlasak
mesh_terms: D001681:Biological Assay; D002460:Cell Line; D000071457:DEAD Box Protein 58; D053487:DEAD-box RNA Helicases / Q000037:antagonists & inhibitors* / Q000378:metabolism; D017930:Genes, Reporter; D006801:Humans; D057131:Immune Evasion; D009982:Gammainfluenzavirus / Q000276:immunology / Q000472:pathogenicity*; D016899:Interferon-beta / Q000037:antagonists & inhibitors* / Q000096:biosynthesis; D008156:Luciferases / Q000235:genetics / Q000378:metabolism; D025941:Protein Interaction Mapping; D011971:Receptors, Immunologic; D017361:Viral Nonstructural Proteins / Q000378:metabolism*; D037521:Virulence Factors / Q000378:metabolism*
chemical_list: C085820:INS1 protein, influenza virus; D011971:Receptors, Immunologic; D017361:Viral Nonstructural Proteins; D037521:Virulence Factors; D016899:Interferon-beta; D008156:Luciferases; C452820:RIGI protein, human; D000071457:DEAD Box Protein 58; D053487:DEAD-box RNA Helicases