Comparative transcriptomic and proteomic analyses proved IFN-λ1 is a more potent inducer of ISGs than IFN-α against porcine epidemic diarrhea virus in porcine intestinal epithelia cells.

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

Type III interferon (IFN-λ) is currently considered to be largely non-redundant to type I interferon (IFN-α) in antivirus infection, especially in epithelia cells. Previous studies reported that, comparing with IFN-α, IFN-λ exhibited stronger induction of interferon stimulated genes (ISGs) at the transcriptional level in intestinal epithelia cells and stronger inhibition of porcine epidemic diarrhea virus (PEDV). In this study, the different mechanisms of ISGs upregulation induced by IFN-α and IFN-λ1 were compared at the mRNA and protein levels in the porcine intestinal epithelial cell model (IPEC-J2). It was proved that IFN-λ1 consistently exhibited stronger stimulation effects at both levels. At the mRNA level, 132 genes were significantly upregulated upon IFN-λ1 stimulation, while 42 genes upon IFN-α stimulation. At the protein level, 47 proteins were significantly upregulated upon IFN-λ1 stimulation, but only 8 proteins were upregulated upon IFN-α stimulation. The shared upregulated genes/proteins by IFN-λ1 in both transcriptional and translational omics, especially the regulation factors of ISG15, were involved in the Jak-STAT signaling pathway. Comparing to IFN-α, IFN-λ1 could induce more consistent up-regulation of the key ISGs (ISG15, USP18, OASL, and RSAD2) post induction from 3 h to 24 h by RT-qPCR validation. It was further confirmed that ISG15 and RSAD2 could inhibit PEDV infection in dose-dependent manners through functional analysis. This study provided the solid evidence that IFN-λ1 could induce more unique and higher ISGs expression level, which exhibited anti-PEDV effects in porcine intestinal epithelial cell.