Journal
PROTEIN & CELL
Volume 9, Issue 9, Pages 799-807Publisher
SPRINGEROPEN
DOI: 10.1007/s13238-018-0511-1
Keywords
interferon-stimulated genes; IFN-beta signaling; PIM1; RIG-I; MDA5
Categories
Funding
- Chinese Academy of Sciences [KFZD-SW-209]
- National Natural Science Foundation of China [81530066]
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Virus infection induces the production of type I interferons (IFNs). IFNs bind to their heterodimeric receptors to initiate downstream cascade of signaling, leading to the up-regulation of interferon-stimulated genes (ISGs). ISGs play very important roles in innate immunity through a variety of mechanisms. Although hundreds of ISGs have been identified, it is commonly recognized that more ISGs await to be discovered. The aim of this study was to identify new ISGs and to probe their roles in regulating virus-induced type I IFN production. We used consensus interferon (Con-IFN), an artificial alpha IFN that was shown to be more potent than naturally existing type I IFN, to treat three human immune cell lines, CEM, U937 and Daudi cells. Microarray analysis was employed to identify those genes whose expressions were up-regulated. Six hundred and seventeen genes were up-regulated more than 3-fold. Out of these 617 genes, 138 were not previously reported as ISGs and thus were further pursued. Validation of these 138 genes using quantitative reverse transcription PCR (qRT-PCR) confirmed 91 genes. We screened 89 genes for those involved in Sendai virus (SeV)-induced IFN-beta promoter activation, and PIM1 was identified as one whose expression inhibited SeV-mediated IFN-beta activation. We provide evidence indicating that PIM1 specifically inhibits RIG-I- and MDA5-mediated IFN-beta signaling. Our results expand the ISG library and identify PIM1 as an ISG that participates in the regulation of virus-induced type I interferon production.
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