Influenza A virus-encoded NS1 virulence factor protein inhibits innate immune response by targeting IKK.

نویسندگان

  • Shijuan Gao
  • Liping Song
  • Jiandong Li
  • Zhenzhu Zhang
  • Haiyan Peng
  • Wei Jiang
  • Qingtao Wang
  • Tiebang Kang
  • Shuai Chen
  • Wenlin Huang
چکیده

The IKK/NF-κB pathway is an essential signalling process initiated by the cell as a defence against viral infection like influenza virus. This pathway is therefore a prime target for viruses attempting to counteract the host response to infection. Here, we report that the influenza A virus NS1 protein specifically inhibits IKK-mediated NF-κB activation and production of the NF-κB induced antiviral genes by physically interacting with IKK through the C-terminal effector domain. The interaction between NS1 and IKKα/IKKβ affects their phosphorylation function in both the cytoplasm and nucleus. In the cytoplasm, NS1 not only blocks IKKβ-mediated phosphorylation and degradation of IκBα in the classical pathway but also suppresses IKKα-mediated processing of p100 to p52 in the alternative pathway, which leads to the inhibition of nuclear translocation of NF-κB and the subsequent expression of downstream NF-κB target genes. In the nucleus, NS1 impairs IKK-mediated phosphorylation of histone H3 Ser 10 that is critical to induce rapid expression of NF-κB target genes. These results reveal a new mechanism by which influenza A virus NS1 protein counteracts host NF-κB-mediated antiviral response through the disruption of IKK function. In this way, NS1 diminishes antiviral responses to infection and, in turn, enhances viral pathogenesis.

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عنوان ژورنال:
  • Cellular microbiology

دوره 14 12  شماره 

صفحات  -

تاریخ انتشار 2012