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Open Access Highly Accessed Short report

Non-structural protein 1 of avian influenza A viruses differentially inhibit NF-κB promoter activation

Muhammad Munir1*, Siamak Zohari12 and Mikael Berg1

Author Affiliations

1 Department of Biomedical Sciences and Veterinary Public Health, Swedish University of Agricultural Sciences (SLU), Ulls väg 2B, SE-751 89 Uppsala, Sweden

2 Department of Virology, Immunobiology and Parasitology, National Veterinary Institute (SVA), Ulls väg 2B, SE-751 89 Uppsala, Sweden

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Virology Journal 2011, 8:383  doi:10.1186/1743-422X-8-383

Published: 2 August 2011

Abstract

Background

Influenza virus infection activates NF-κB and is a general prerequisite for a productive influenza virus infection. On the other hand, non-structural protein 1 (NS1) suppresses this viral activated NF-κB, presumably to prevent expression of NF-κB mediated anti-viral response. NS1 proteins of influenza A viruses are divided into two groups, known as allele A and allele B. The possible functional relevance of this NS1 division to viral pathogenicity is lacking.

Findings

The ability of NS1 protein from two avian influenza subtypes, H6N8 and H4N6, to inhibit NF-κB promoter activation was assessed. Further, efforts were made to characterize the genetic basis of this inhibition. We found that allele A NS1 proteins of H6N8 and H4N6 are significantly better in preventing dsRNA induced NF-κB promoter activation compared to allele B of corresponding subtypes, in a species independent manner. Furthermore, the ability to suppress NF-κB promoter activation was mapped to the effector domain while the RNA binding domain alone was unable to suppress this activation. Chimeric NS1 proteins containing either RNA binding domain of allele A and effector domain of allele B or vice versa, were equally potent in preventing NF-κB promoter activation compared to their wt. NS1 protein of allele A and B from both subtypes expressed efficiently as detected by Western blotting and predominantly localized in the nucleus in both A549 and MiLu cells as shown by in situ PLA.

Conclusions

Here, we present another aspect of NS1 protein in inhibiting dsRNA induced NF-κB activation in an allele dependent manner. This suggests a possible correlation with the virus's pathogenic potential.

Keywords:
NS1 protein; avian influenza virus; NF-κB; allele A; allele B