Porcine epidemic diarrhea virus inhibits dsRNA-induced interferon-β production in porcine intestinal epithelial cells by blockade of the RIG-I-mediated pathway.
BACKGROUND
The lack of optimal porcine cell lines has severely impeded the study and progress in elucidation of porcine epidemic diarrhea virus (PEDV) pathogenesis. Vero cell, an African green monkey kidney cell line, was often used to isolate and propagate PEDV. Nonetheless, the target cells of PEDV in vivo are intestinal epithelial cells, during infection, intestinal epithelia would be damaged and resulted in digestive disorders. The immune functions of porcine epithelial cells and interactions with other immune cell populations display a number of differences compared to other species. Type I interferon (IFN) plays an important role in antiviral immune response. Limited reports showed that PEDV could inhibit type I interferon production. In this study, porcine small intestinal epithelial cells (IECs), the target cells of PEDV, were used as the infection model in vitro to identify the possible molecular mechanisms of PEDV-inhibition IFN-β production.


RESULTS
PEDV not only failed to induce IFN-β expression, but also inhibited dsRNA-mediated IFN-β production in IECs. As the key IFN-β transcription factors, we found that dsRNA-induced activation of IFN regulatory factor 3 (IRF-3) was inhibited after PEDV infection, but not nuclear factor-kappaB (NF-κB). To identify the mechanism of PEDV intervention with dsRNA-mediated IFN-β expression more accurately, the role of individual molecules of RIG-I signaling pathway were investigated. In the upstream of IRF-3, TANK-binding kinase 1 (TBK1)-or inhibitor of κB kinase-ε (IKKε)-mediated IFN-β production was not blocked by PEDV, while RIG-I-and its adapter molecule IFN-β promoter stimulator 1 (IPS-1)-mediated IFN-β production were completely inhibited after PEDV infection.


CONCLUSIONS
Taken together, our data demonstrated for the first time that PEDV infection of its target cell line, IECs, inhibited dsRNA-mediated IFN-β production by blocking the activation of IPS-1 in RIG-I-mediated pathway. Our studies offered new visions in understanding of the interaction between PEDV and host innate immune system.
College of Veterinary Medicine, Northeast Agricultural University, 59 Mucai Street, Xiangfang District, Harbin, 150030, China. liyancao2011@163.com.
Liyan
L
Cao
College of Veterinary Medicine, Northeast Agricultural University, 59 Mucai Street, Xiangfang District, Harbin, 150030, China. 675905170@qq.com.
Xuying
X
Ge
College of Veterinary Medicine, Northeast Agricultural University, 59 Mucai Street, Xiangfang District, Harbin, 150030, China. 654833290@qq.com.
Yu
Y
Gao
Institute of Virology University of Veterinary Medicine, BÜnteweg 17, D-30559, Hannover, Germany. Georg.Herrler@tiho-hannover.de.
Georg
G
Herrler
College of Electrical and Information, Northeast Agricultural University, Harbin, 150030, China. rdren@neau.edu.cn.
Yudong
Y
Ren
College of Veterinary Medicine, Northeast Agricultural University, 59 Mucai Street, Xiangfang District, Harbin, 150030, China. renxf@neau.edu.cn.
Xiaofeng
X
Ren
College of Veterinary Medicine, Northeast Agricultural University, 59 Mucai Street, Xiangfang District, Harbin, 150030, China. ligx@neau.edu.cn.
Guangxing
G
Li
D000818:Animals; D002460:Cell Line; D002522:Chlorocebus aethiops; D018352:Coronavirus Infections / Q000378:metabolism / Q000821:virology; D004847:Epithelial Cells; D050838:Interferon Regulatory Factor-3 / Q000378:metabolism; D016899:Interferon-beta / Q000096:biosynthesis*; D007413:Intestinal Mucosa / Q000378:metabolism* / Q000821:virology*; D016328:NF-kappa B / Q000378:metabolism; D011070:Poly I-C / Q000494:pharmacology; D053485:Porcine epidemic diarrhea virus / Q000502:physiology*; D012330:RNA, Double-Stranded / Q000378:metabolism*; D015398:Signal Transduction; D013552:Swine; D014709:Vero Cells
D050838:Interferon Regulatory Factor-3; D016328:NF-kappa B; D012330:RNA, Double-Stranded; D016899:Interferon-beta; D011070:Poly I-C