IFN-Lambda 3 Mediates Antiviral Protection Against Porcine Epidemic Diarrhea Virus by Inducing a Distinct Antiviral Transcript Profile in Porcine Intestinal Epithelia

文献类型： 外文期刊

第一作者： Li, Liang

作者： Li, Liang;Xue, Mei;Fu, Fang;Yin, Lingdan;Feng, Li;Liu, Pinghuang

作者机构：

关键词： interferon-lambda 3; interferon alpha; RNA-seq; enteroids; PEDV

期刊名称：FRONTIERS IN IMMUNOLOGY （ 影响因子：7.561； 五年影响因子：7.624 ）

ISSN： 1664-3224

年卷期： 2019 年 10 卷

页码：

收录情况： SCI

摘要： Type III interferon-lambda (IFN-lambda) plays a critical role against infection, particularly in mucosal infection in the respiratory and gastrointestinal tract. Our study and other previous studies have shown that porcine IFN-l more efficiently curtails the infection of porcine epidemic diarrhea virus (PEDV) in the intestine epithelia than type I IFN, whereas IFN-lambda 3 exerts a more potent effect than IFN-lambda 1. However, the underlying mechanism remains elusive, and in particular, the transcriptional profile induced by IFN-lambda 3 has not been reported. Here, to resolve the mechanism responsible for the disparity between IFN-alpha 3 and type I IFN in anti-mucosal virus infection, we compared the transcription profiles induced by the two IFNs in porcine intestinal epithelial (IPEC-J2) cells by RNA-Seq. Our results showed that the pretreatment of IPEC-J2 cells with IFN-lambda 3 resulted in the differential expression of 983 genes. In contrast, IFN-alpha only modified the expression of 134 genes, and 110 of these genes were also observed in the response to IFN-lambda 3. A transcriptional enrichment analysis indicated that IFN-lambda 3 or IFN-alpha regulates multiple cellular processes and that IFN-lambda 3 activates more robust signaling pathways, particularly the antiviral Jak-STAT signaling pathway, than IFN-alpha. Furthermore, we verified the RNA-Seq results through an RT-qPCR analysis of IPEC-J2 cells and porcine enteroids. Moreover, transient expression of the porcine rsad2 and mx2 genes among the top 10 genes induced by IFN-lambda 3 significantly inhibited PEDV infection. Collectively, the data showed that IFN-lambda 3 induces a unique transcriptional profile that does not completely overlap with that induced by IFN-alpha and strongly elicits a set of genes responsible for the antiviral activity of IFN-lambda 3. These findings provide important knowledge regarding the elicited ISGs of type I and III IFNs in restricting porcine intestinal viral infection.

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