IL-22 suppresses the infection of porcine enteric coronaviruses and rotavirus by activating STAT3 signal pathway

• Published in: Antiviral research Vol. 142; pp. 68 - 75
• Main Authors: Xue, Mei, Zhao, Jing, Ying, Lan, Fu, Fang, Li, Lin, Ma, Yanlong, Shi, Hongyan, Zhang, Jiaoer, Feng, Li, Liu, Pinghuang
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 01.06.2017
• Subjects: Amino Acid Sequence; Aminosalicylic Acids - metabolism; Animals; Benzenesulfonates - metabolism; beta-Defensins - metabolism; Cell Line; Chlorocebus aethiops; Cloning, Molecular; Coronavirus - drug effects; Coronavirus Infections - drug therapy; Coronavirus Infections - virology; Cytokines; Diarrhea - drug therapy; Diarrhea - virology; Epithelial Cells - virology; Gene Expression Regulation; Genes, Viral; Interleukin 22; Interleukin-18 - metabolism; Interleukins - genetics; Interleukins - pharmacology; Intestinal epithelia; Mutation; Phylogeny; Porcine epidemic diarrhea virus; Porcine epidemic diarrhea virus - drug effects; Porcine rotavirus; Recombinant Proteins - genetics; Rotavirus - drug effects; Rotavirus Infections - drug therapy; Rotavirus Infections - virology; Sequence Alignment; Sequence Homology; Signal Transduction - drug effects; STAT3; STAT3 Transcription Factor - drug effects; Swine; Transmissible gastroenteritis virus; Transmissible gastroenteritis virus - drug effects; Vero Cells; Intestinal epithelia; Interleukin 22; Transmissible gastroenteritis virus; Porcine epidemic diarrhea virus; Porcine rotavirus; STAT3
• ISSN: 0166-3542; 1872-9096; 1872-9096
• DOI: 10.1016/j.antiviral.2017.03.006

Interleukin-22 (IL-22), a member of the IL-10 superfamily, plays essential roles in fighting against mucosal microbial infection and maintaining mucosal barrier integrity within the intestine. However, little knowledge exists on the ability of porcine IL-22 (pIL-22) to fight against viral infection in the gut. In this study, we found that recombinant mature pIL-22 (mpIL-22) inhibited the infection of multiple diarrhea viruses, including alpha coronavirus, porcine epidemic diarrhea virus (PEDV), transmissible gastroenteritis virus (TGEV), and porcine rotavirus (PoRV), in the intestinal porcine epithelial cell line J2 (IPEC-J2) cells. mpIL-22 up-regulated the expression of the antimicrobial peptide beta-defensin (BD-2), cytokine IL-18 and IFN-λ. Furthermore, we found that mpIL-22 induced phosphorylation of STAT3 on Ser727 and Tyr705 in IPEC-J2 cells. Inhibition of STAT3 phosphorylation by S3I-201 abrogated the antiviral ability of mpIL-22 and the mpIL-22-induced expression of BD-2, IL-18, and IFN-λ. Together, mpIL-22 inhibited the infection of PoRV and enteric coronaviruses, and up-regulated the expression of antimicrobial genes in IPEC-J2, which were mediated by the activation of the STAT3 signal pathway. The significant antiviral activity of IL-22 to curtail multiple enteric diarrhea viruses in vitro suggests that pIL-22 could be a novel therapeutic against devastating viral diarrhea in piglets. •Porcine IL-22 inhibits the most common three porcine diarrhea viruses (rotavirus, PEDV and TGEV) in vitro.•STAT3 signaling by IL-22 accounts for the antiviral activity and the enhanced expression of protective genes of mpIL-22.•IL-22 could provide a novel approach to control devastating viral diarrhea in piglets.