Comparative Transcriptomic and Proteomic Analyses Prove that IFN-λ1 is a More Potent Inducer of ISGs than IFN‑α against Porcine Epidemic Diarrhea Virus in Porcine Intestinal Epithelial Cells

Type
III interferon (IFN-λ) is currently considered to be largely
nonredundant to
type I interferon (IFN-α) in antivirus infection, especially
in epithelial cells. Previous studies reported that, compared with
IFN-α, IFN-λ 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-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. Compared to IFN-α, IFN-λ1 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-λ1 could induce a more unique and higher ISG expression
level, which exhibited anti-PEDV effects on porcine intestinal epithelial
cells.