Non-structural protein 1 （NS1） of the influenza virus plays a crucial role in modulating the host immune response and facili- tating virus replication. The formation of a homodimer or an oligomer is necessary for NSI to exert its function efficiently. In the present study, the NS 1 protein from the A/Shantou/602/06（H3N2） virus （herein abbreviated as NS32） was found to interact with NS1 from A/Shantou/169/O6（H1N1）, A/Chicken/Guangdong/1/05（HSN1） and A/Quail/Hong Kong/G1/97（H9N2） （abbre- viated as NS11, NS51 and NS92, respectively） viruses, although NS32 shares 17.4%-20.9% sequence diversity with NS11, NS51 and NS92. This indicates that the heterologous interactions between NS1 proteins from different influenza A virus sub- types/strains may be a common event during co-infection.
LI WeiZhongZHANG HengWANG GeFeiZHANG ChiZENG XiangXingLIU HuiCHEN XiaoXuanXU YanXuanLI KangSheng
Non-structural protein 1(NS1)is an important virulence factor of the highly pathogenic H5N1 avian influenza virus.A five-amino-acid(5 aa)deletion at position 80–84 and an aspartic acid to glutamic acid substitution at position 92(D92E)are two major NS1 mutations that are highly correlated with enhanced virulence.To investigate the effect of these mutations in H5N1 virulence,three H5N1-NS1 variants were constructed:NS51(lacking 5 aa at position 80–84),NS51(I)(carrying a 5-aa insertion at position 80–84)and NS51(IM)(carrying both the 5-aa insertion and the D92E mutation).We examined the effects of these mutations on interferon(IFN)induction,tumor-necrosis factor(TNF)a response,p53 activity and apoptosis.We found that the D92E mutation eliminated NS1’s repressive effect on IFN induction,while the 5-aa deletion resulted in enhanced resistance to TNFa responses.We also observed that all three variants exhibited a similar suppressive effect on p53 transcriptional activity,although none of them significantly influenced apoptosis of host cells.Our findings shed new light on the role of NS1 in the pathogenicity of H5N1 virus.
