Differential RNA silencing suppression activity of NS1 proteins from different influenza A virus strains.
The NS1 gene of influenza A virus encodes a multi-functional protein that plays an important role in counteracting cellular antiviral mechanisms such as the interferon (IFN), protein kinase R and retinoic acid-inducible gene product I pathways. In addition, NS1 has recently been shown to have RNA interference (RNAi) or RNA silencing suppression (RSS) activity. This study analysed the IFN antagonistic activity of NS1 and the RSS activity for several influenza subtypes: H1N1, H3N2, H5N1 and H7N7. It was shown that the various NS1 proteins were capable of inhibiting the activation of an IFN-responsive promoter. However, differential RSS activity was measured among the NS1 variants. The NS1 protein of strain A/WSN/33 (H1N1) was most potent in suppressing short hairpin RNA-mediated gene silencing. In contrast, NS1 proteins of the highly pathogenic H5N1 strains A/VN/1194/04 and A/HK/156/97 were most potent in complementing the RSS function of the human immunodeficiency virus type 1 Tat protein. These results show that the ability of NS1 to suppress RNAi varies among influenza strains and is likely to contribute to differences in viral replication capacity and pathogenicity.
Laboratory of Experimental Virology, Department of Medical Microbiology, Center for Infection and Immunity Amsterdam (CINIMA), Academic Medical Center, University of Amsterdam, Meibergdreef 15, 1105 AZ Amsterdam, The Netherlands.
Walter
W
de Vries
Laboratory of Experimental Virology, Department of Medical Microbiology, Center for Infection and Immunity Amsterdam (CINIMA), Academic Medical Center, University of Amsterdam, Meibergdreef 15, 1105 AZ Amsterdam, The Netherlands.
Joost
J
Haasnoot
Department of Virology and National Influenza Center, Erasmus Medical Center, Dr Molewaterplein 50, 30015 GE Rotterdam, The Netherlands.
Ron
R
Fouchier
Phytovation B.V., Wassenaarseweg 72, 2333 AL Leiden, The Netherlands.
Peter
P
de Haan
Laboratory of Experimental Virology, Department of Medical Microbiology, Center for Infection and Immunity Amsterdam (CINIMA), Academic Medical Center, University of Amsterdam, Meibergdreef 15, 1105 AZ Amsterdam, The Netherlands.
Ben
B
Berkhout
D006801:Humans; D007108:Immune Tolerance; D053118:Influenza A Virus, H1N1 Subtype / Q000276:immunology; D053122:Influenza A Virus, H3N2 Subtype / Q000276:immunology; D053124:Influenza A Virus, H5N1 Subtype / Q000276:immunology; D053126:Influenza A Virus, H7N7 Subtype / Q000276:immunology; D009980:Influenza A virus / Q000276:immunology*; D007251:Influenza, Human / Q000276:immunology / Q000821:virology*; D007372:Interferons / Q000037:antagonists & inhibitors*; D034622:RNA Interference; D017361:Viral Nonstructural Proteins / Q000276:immunology*; D054322:tat Gene Products, Human Immunodeficiency Virus / Q000276:immunology
C085820:INS1 protein, influenza virus; D017361:Viral Nonstructural Proteins; D054322:tat Gene Products, Human Immunodeficiency Virus; D007372:Interferons