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Non-structural protein 1 of avian influenza A viruses differentially inhibit NF-kappaB promoter activation
Muhammad Munir, Siamak Zohari and Mikael Berg
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Virology Journal 2011, 8:383 doi:10.1186/1743-422X-8-383
Published: 2 August 2011
Abstract (provisional)
Background
Influenza virus infection activates NF-kappaB 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-kappaB, presumably to prevent expression of NF-kappaB 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-kappaB 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-kappaB promoter activation compared to allele B of corresponding subtypes, in a species independent manner. Furthermore, the ability to suppress NF-kappaB 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-kappaB 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-kappaB activation in an allele dependent manner. This suggests a possible correlation with the virus's pathogenic potential.
Muhammad Munir, Siamak Zohari and Mikael Berg
For all author emails, please log on.
Virology Journal 2011, 8:383 doi:10.1186/1743-422X-8-383
Published: 2 August 2011
Abstract (provisional)
Background
Influenza virus infection activates NF-kappaB 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-kappaB, presumably to prevent expression of NF-kappaB 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-kappaB 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-kappaB promoter activation compared to allele B of corresponding subtypes, in a species independent manner. Furthermore, the ability to suppress NF-kappaB 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-kappaB 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-kappaB activation in an allele dependent manner. This suggests a possible correlation with the virus's pathogenic potential.
