The accessory protein ORF3 of porcine epidemic diarrhea virus inhibits cellular interleukin-6 and interleukin-8 productions by blocking the nuclear factor-κB p65 activation

• Published in: Veterinary microbiology Vol. 251; p. 108892
• Main Authors: Wu, Zhijun, Cheng, Lixin, Xu, Jiaxin, Li, Pengfei, Li, Xingzhi, Zou, Dehua, Zhang, Yating, Wang, Xianhe, Wu, Xuening, Shen, Yujiang, Li, Yuchang, Yao, Lili, Guo, Dexuan, Li, Liyang, Xiao, Lijie, Song, Baifen, Ma, Jinzhu, Liu, Xinyang, Xu, Shuyan, Xu, Xin, Zhang, Hua, Zheng, Liang, Cao, Hongwei
• Format: Journal Article
• Language: English
• Published: Amsterdam Elsevier B.V 01.12.2020; Elsevier BV
• Subjects: antagonists; Cytokines; Diarrhea; Epidemics; Inflammation; Innate immune; Interleukin 6; Interleukin 8; Molecular modelling; NF-κB; NF-κB protein; Nuclear transport; ORF3 protein; Phosphorylation; Porcine epidemic diarrhea virus; Pro-inflammatory cytokine; Proteins; RNA viruses; Transmissible gastroenteritis; viruses; Pro-inflammatory cytokine; NF-κB; Innate immune; Porcine epidemic diarrhea virus; ORF3 protein
• ISSN: 0378-1135; 1873-2542; 1873-2542
• DOI: 10.1016/j.vetmic.2020.108892

•PEDV ORF3 inhibits the productions of pro-inflammatory cytokines IL-6 and IL-8.•PEDV ORF3 inhibits NF-κB activation through blockage of p65 activation.•Our study links PEDV ORF3 to inhibition of pro-inflammatory cytokines. Porcine epidemic diarrhea virus (PEDV) is an enveloped, single-stranded positive-sense RNA virus that belongs to a porcine entero-pathogenic alphacoronavirus, causing lethal watery diarrhea in piglets. Despite existing study reports the sole accessory protein ORF3 identified as NF-κB antagonist, the contribution of PEDV ORF3 to production of the pro-inflammatory cytokines mediated by NF-κB signaling remains largely unknown. Thus in this present study, we showed that PEDV ORF3 protein significantly inhibited the productions of pro-inflammatory cytokines interleukin-6 (IL-6) and IL-8. The phosphorylation of IκBα was inhibited by ORF3 protein, but no degradation of IκBα was induced in ORF3-expressing cells. Furthermore, PEDV ORF3 inhibited NF-κB activation through preventing nuclear factor p65 phosphorylation and down-regulating p65 expression level, as well as interfering nuclear translocation of p65, eventually resulting into the inhibition of IL-6 and IL-8 production. Our study definitely links PEDV ORF3 to inhibition of pro-inflammatory cytokines production, which will provide new insight into the molecular mechanisms of NF-κB activity inhibited by PEDV proteins to facilitate virus evasion of host innate immune.