Inhibition of Type I Interferon Production via Suppressing IKK-Gamma Expression: A New Strategy for Counteracting Host Antiviral Defense by Influenza A Viruses?

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• 作者：Yimeng Wang ; Jianhong Zhou ; Chuanmin Ruan ; Yuchun Du
• 刊名：Journal of Proteome Research
• 出版年：2012
• 出版时间：January 1, 2012
• 年：2012
• 卷：11
• 期：1
• 页码：217-223
• 全文大小：875K
• 年卷期：v.11,no.1(January 1, 2012)
• ISSN：1535-3907

文摘

Blockage of the induction of type I interferons (IFNs) is essential for the success of influenza virus proliferation in host cells. Several molecular mechanisms by which influenza viruses inhibit IFN induction have been characterized. Here we report a potentially new strategy influenza viruses employ to inhibit IFN production during viral infection. Through a two-dimensional gel electrophoresis based proteomic approach, we found that the expression of I魏B kinase-gamma (IKK纬) was suppressed by influenza A virus infection in human lung epithelial A549 cells. Silencing of cellular IKK纬 by small interfering RNA led to enhanced replication of influenza viruses. Concomitantly, overexpression of IKK纬 resulted in increased production of IFN伪/尾, whereas influenza virus infection completely eliminated the IKK纬-overexpression-induced production of IFN伪/尾. Our results suggest that IKK纬 and influenza virus are mutually inhibitory, and influenza viruses may inhibit IFN production through suppressing the expression of IKK纬 during viral infection.

Keywords:

Influenza virus; H1N1; interferon; IKK纬; NF-魏B; 2-DE; proteomics; protein expression; LC-MS/MS