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Effects of NS1 variants of H5N1 influenza virus on interferon induction, TNFα response and p53 activity

Cellular & Molecular Immunology volume 7, pages 235–242 (2010)Cite this article

Abstract

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)α 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 TNFα 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.

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Acknowledgements

We are grateful to Dr William Ba-Thein for helpful discussion and editing of the manuscript. We thank Dr Xu Liyan for the use of a TD20/20 luminometer. This work was supported by the National Natural Science Foundation of China (No. 30771988and No. 30972766), Specialized Research Fund for the Doctoral Program of Higher Education (No. 20094402110004), Guangdong Natural Science Foundation (No. 8151503102000022 and 9451503102003499), Outstanding Young Scientists Foundation of Guangdong Province Education Department (No. LYM08056), State Key Lab of Agriculture Microbiology Open Foundation (No. AML200910) and Shantou University Medical College Research Foundation.

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  1. These authors contributed equally to this work.

  2. Dr K S Li, Department of Microbiology and Immunology, Key Immunopathology Laboratory of Guangdong Province, Shantou University Medical College, Shantou 515041, China. E-mail: ksli@stu.edu.cn

Authors and Affiliations

  1. Department of Microbiology and Immunology, Key Immunopathology Laboratory of Guangdong Province, Shantou University Medical College, Shantou, China

    Weizhong Li, Gefei Wang, Heng Zhang, Gang Xin, Dangui Zhang, Jun Zeng, Xiaoxuan Chen, Yanxuan Xu, Youhong Cui & Kangsheng Li

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Li, W., Wang, G., Zhang, H. et al. Effects of NS1 variants of H5N1 influenza virus on interferon induction, TNFα response and p53 activity. Cell Mol Immunol 7, 235–242 (2010). https://doi.org/10.1038/cmi.2010.6

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