title: Inhibition of type I interferon production via suppressing IKK-gamma expression: a new strategy for counteracting host antiviral defense by influenza A viruses?
abstract: 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 IκB kinase-gamma (IKKγ) was suppressed by influenza A virus infection in human lung epithelial A549 cells. Silencing of cellular IKKγ by small interfering RNA led to enhanced replication of influenza viruses. Concomitantly, overexpression of IKKγ resulted in increased production of IFNα/β, whereas influenza virus infection completely eliminated the IKKγ-overexpression-induced production of IFNα/β. Our results suggest that IKKγ and influenza virus are mutually inhibitory, and influenza viruses may inhibit IFN production through suppressing the expression of IKKγ during viral infection.
authors: Department of Biological Sciences, SCEN 601, University of Arkansas, Fayetteville, Arkansas 72701, United States.
authors: Yimeng
authors: Y
authors: Wang
authors: Jianhong
authors: J
authors: Zhou
authors: Chuanmin
authors: C
authors: Ruan
authors: Yuchun
authors: Y
authors: Du
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D004285:Dogs; D015180:Electrophoresis, Gel, Two-Dimensional; D005786:Gene Expression Regulation; D057809:HEK293 Cells; D006801:Humans; D051550:I-kappa B Kinase / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D057131:Immune Evasion; D009980:Influenza A virus / Q000276:immunology / Q000502:physiology*; D007251:Influenza, Human / Q000276:immunology / Q000378:metabolism* / Q000821:virology; D016898:Interferon-alpha / Q000235:genetics / Q000378:metabolism*; D016899:Interferon-beta / Q000235:genetics / Q000378:metabolism*; D008969:Molecular Sequence Data; D010446:Peptide Fragments / Q000737:chemistry; D053719:Tandem Mass Spectrometry; D014779:Virus Replication
chemical_list: D016898:Interferon-alpha; D010446:Peptide Fragments; D016899:Interferon-beta; D051550:I-kappa B Kinase