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: Karin Pachler, Reinhard Vlasak
• Journal: Virology journal (Virol J) Vol. 8 Pg. 48 (Feb 02 2011) ISSN: 1743-422X [Electronic] England
• PMID: 21288362 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• INS1 protein, influenza virus
• Receptors, Immunologic
• Viral Nonstructural Proteins
• Virulence Factors
• Interferon-beta
• Luciferases
• DDX58 protein, human
• DEAD Box Protein 58
• DEAD-box RNA Helicases

Topics

• Biological Assay
• Cell Line
• DEAD Box Protein 58
• DEAD-box RNA Helicases (antagonists & inhibitors, metabolism)
• Genes, Reporter
• Humans
• Immune Evasion
• Influenzavirus C (immunology, pathogenicity)
• Interferon-beta (antagonists & inhibitors, biosynthesis)
• Luciferases (genetics, metabolism)
• Protein Interaction Mapping
• Receptors, Immunologic
• Viral Nonstructural Proteins (metabolism)
• Virulence Factors (metabolism)