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Published online ahead of print on 15 April 2009 as doi:10.1099/vir.0.008284-0
Journal of General Virology 2009;90:1916.

A more recent version of this article appeared on August 1, 2009 J Gen Virol (2009), DOI 10.1099/vir.0.008284-0
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Differential RNA silencing suppression activity of NS1 proteins from different influenza A strains

Walter de Vries1, Joost Haasnoot1, Ron Fouchier2, Peter de Haan3 and Ben Berkhout1,4

1 Academic Medical Center of the University of Amsterdam;
2 Virology, Erasmus MC;
3 Phytovation

4 E-mail: b.berkhout{at}amc.uva.nl

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 (PKR) and retinoic acid-inducible gene product I (RIG-I) pathways. In addition, NS1 has recently been shown to have RNA interference (RNAi) or RNA silencing suppression (RSS) activity. Here we studied the IFN antagonistic activity of NS1 and the RSS activity for several influenza subtypes: H1N1, H3N2, H5N1 and H7N7. We show that the various NS1 proteins are capable of inhibiting the activation of an IFN responsive promoter. However, we measured differential RSS activity among the NS1 variants. The NS1 protein of strain A/WSN/33 (H1N1) is most potent in suppressing short hairpin RNA (shRNA) mediated gene silencing. In contrast, NS1 proteins of the highly pathogenic H5N1 strains A/VN/1194/04 and A/HK/156/97 are most potent in complementing the RSS function of the HIV-1 Tat protein. These results show that the ability of NS1 to suppress RNAi varies among influenza strains, which is likely to contribute to differences in viral replication capacity and pathogenicity.

Received 28 October 2008; accepted 9 April 2009.




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