IL-22 suppresses the infection of porcine enteric coronaviruses and rotavirus by activating STAT3 signal pathway.
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.
State Key Laboratory of Veterinary Biotechnology, Harbin Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Harbin, 150069, China.
Mei
M
Xue
College of Agriculture and Animal Husbandry, Qinghai University, Xining, 810003, China.
Jing
J
Zhao
College of Agriculture and Animal Husbandry, Qinghai University, Xining, 810003, China.
Lan
L
Ying
State Key Laboratory of Veterinary Biotechnology, Harbin Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Harbin, 150069, China.
Fang
F
Fu
State Key Laboratory of Veterinary Biotechnology, Harbin Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Harbin, 150069, China.
Lin
L
Li
State Key Laboratory of Veterinary Biotechnology, Harbin Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Harbin, 150069, China.
Yanlong
Y
Ma
State Key Laboratory of Veterinary Biotechnology, Harbin Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Harbin, 150069, China.
Hongyan
H
Shi
State Key Laboratory of Veterinary Biotechnology, Harbin Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Harbin, 150069, China.
Jiaoer
J
Zhang
State Key Laboratory of Veterinary Biotechnology, Harbin Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Harbin, 150069, China. Electronic address: fengli_h@163.com.
Li
L
Feng
State Key Laboratory of Veterinary Biotechnology, Harbin Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Harbin, 150069, China. Electronic address: liupinghuang@caas.cn.
Pinghuang
P
Liu
D000595:Amino Acid Sequence; D000636:Aminosalicylic Acids / Q000378:metabolism; D000818:Animals; D001557:Benzenesulfonates / Q000378:metabolism; D002460:Cell Line; D002522:Chlorocebus aethiops; D003001:Cloning, Molecular; D017934:Coronavirus / Q000187:drug effects*; D018352:Coronavirus Infections / Q000188:drug therapy / Q000821:virology; D016207:Cytokines; D003967:Diarrhea / Q000188:drug therapy / Q000821:virology; D004847:Epithelial Cells / Q000821:virology; D005786:Gene Expression Regulation; D005814:Genes, Viral; D020382:Interleukin-18 / Q000378:metabolism; D007378:Interleukins / Q000235:genetics / Q000494:pharmacology*; D009154:Mutation; D010802:Phylogeny; D053485:Porcine epidemic diarrhea virus / Q000187:drug effects; D011994:Recombinant Proteins / Q000235:genetics; D012401:Rotavirus / Q000187:drug effects*; D012400:Rotavirus Infections / Q000188:drug therapy / Q000821:virology; D050796:STAT3 Transcription Factor / Q000187:drug effects*; D016415:Sequence Alignment; D017385:Sequence Homology; D015398:Signal Transduction / Q000187:drug effects*; D013552:Swine; D005760:Transmissible gastroenteritis virus / Q000187:drug effects; D014709:Vero Cells; D023083:beta-Defensins / Q000378:metabolism; D000097043:Interleukin-22
D000636:Aminosalicylic Acids; D001557:Benzenesulfonates; D016207:Cytokines; D020382:Interleukin-18; D007378:Interleukins; D011994:Recombinant Proteins; D050796:STAT3 Transcription Factor; D023083:beta-Defensins; D000097043:Interleukin-22; C520337:NSC 74859
Interleukin 22; Intestinal epithelia; Porcine epidemic diarrhea virus; Porcine rotavirus; STAT3; Transmissible gastroenteritis virus