Comparative Transcriptomic and Proteomic Analyses Prove that IFN-lambda 1 is a More Potent Inducer of ISGs than IFN-alpha against Porcine Epidemic Diarrhea Virus in Porcine Intestinal Epithelial Cells

文献类型: 外文期刊

第一作者: Zhao, Mingzhi

作者: Zhao, Mingzhi;Ren, Suping;Jiang, Xingwei;Gao, Fenghua;Bai, Shanshan;Yu, Qun;Zhao, Mingzhi;Liu, Hongyu;Xu, Hongwei;Zhang, Liying;Li, Liang;Liu, Pinghuang;Zhai, Linhui;Yue, Qi;Tan, Minjia;Yue, Qi;Tan, Minjia;Li, Honghao;Zhang, Ying

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关键词: intestinal epithelial cell; IFN-lambda 1; IFN-alpha; anti-PEDV; transcriptomics; proteomics

期刊名称:JOURNAL OF PROTEOME RESEARCH ( 影响因子:4.466; 五年影响因子:4.352 )

ISSN: 1535-3893

年卷期: 2020 年 19 卷 9 期

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收录情况: SCI

摘要: Type III interferon (IFN-lambda) is currently considered to be largely nonredundant to type I interferon (IFN-alpha) in antivirus infection, especially in epithelial cells. Previous studies reported that, compared with IFN-alpha, IFN-lambda exhibited stronger induction of interferon-stimulated genes (ISGs) at the transcriptional level in intestinal epithelial cells and stronger inhibition of porcine epidemic diarrhea virus (PEDV). In this study, the different mechanisms of ISG upregulation induced by IFN-alpha and IFN-lambda 1 were compared at the mRNA and protein levels in the porcine intestinal epithelial cell model (IPEC-J2). It was proved that IFN-lambda 1 consistently exhibited stronger stimulation effects at both levels. At the mRNA level, 132 genes were significantly upregulated upon IFN-lambda 1 stimulation, while 42 genes upon IFN-alpha stimulation. At the protein level, 47 proteins were significantly upregulated upon IFN-lambda 1 stimulation, but only 8 proteins were upregulated upon IFN-alpha stimulation. The shared upregulated genes/proteins by IFN-lambda 1 in both transcriptional and translational omics, especially the regulation factors of ISG15, were involved in the JAK-STAT signaling pathway. Compared to IFN-alpha, IFN-lambda 1 could induce more consistent upregulation of the key ISGs (ISG15, USP18, OASL, and RSAD2) at 3-24 h postinduction as measured by reverse transcription-quantitative polymerase chain reaction (RT-qPCR) validation. It was further confirmed through functional analysis that ISG15 and RSAD2 could inhibit PEDV infection in dose-dependent manners. This study provided solid evidence that IFN-lambda 1 could induce a more unique and higher ISG expression level, which exhibited anti-PEDV effects on porcine intestinal epithelial cells.

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