Identification of key proteins of cytopathic biotype bovine viral diarrhoea virus involved in activating NF-κB pathway in BVDV-induced inflammatory response
Wenlu Fan,
Yixin Wang,
Sheng Jiang,
Yuan Li,
Xin Yao,
Mei Wang,
Jinghua Zhao,
Xiaobo Sun,
Xiaoxia Jiang,
Linhan Zhong,
Yanyan Han,
Houhui Song,
Yigang Xu
Affiliations
Wenlu Fan
Key Laboratory of Applied Technology on Green-Eco-Healthy Animal Husbandry of Zhejiang Province, College of Animal Science & Technology, College of Veterinary Medicine, Zhejiang A&F University, Hangzhou, P.R. China
Yixin Wang
Key Laboratory of Applied Technology on Green-Eco-Healthy Animal Husbandry of Zhejiang Province, College of Animal Science & Technology, College of Veterinary Medicine, Zhejiang A&F University, Hangzhou, P.R. China
Sheng Jiang
Key Laboratory of Applied Technology on Green-Eco-Healthy Animal Husbandry of Zhejiang Province, College of Animal Science & Technology, College of Veterinary Medicine, Zhejiang A&F University, Hangzhou, P.R. China
Yuan Li
Key Laboratory of Applied Technology on Green-Eco-Healthy Animal Husbandry of Zhejiang Province, College of Animal Science & Technology, College of Veterinary Medicine, Zhejiang A&F University, Hangzhou, P.R. China
Xin Yao
College of Veterinary Medicine, Northeast Agricultural University, Harbin, P.R. China
Mei Wang
Key Laboratory of Applied Technology on Green-Eco-Healthy Animal Husbandry of Zhejiang Province, College of Animal Science & Technology, College of Veterinary Medicine, Zhejiang A&F University, Hangzhou, P.R. China
Jinghua Zhao
Key Laboratory of Applied Technology on Green-Eco-Healthy Animal Husbandry of Zhejiang Province, College of Animal Science & Technology, College of Veterinary Medicine, Zhejiang A&F University, Hangzhou, P.R. China
Xiaobo Sun
Key Laboratory of Applied Technology on Green-Eco-Healthy Animal Husbandry of Zhejiang Province, College of Animal Science & Technology, College of Veterinary Medicine, Zhejiang A&F University, Hangzhou, P.R. China
Xiaoxia Jiang
Key Laboratory of Applied Technology on Green-Eco-Healthy Animal Husbandry of Zhejiang Province, College of Animal Science & Technology, College of Veterinary Medicine, Zhejiang A&F University, Hangzhou, P.R. China
Linhan Zhong
Key Laboratory of Applied Technology on Green-Eco-Healthy Animal Husbandry of Zhejiang Province, College of Animal Science & Technology, College of Veterinary Medicine, Zhejiang A&F University, Hangzhou, P.R. China
Yanyan Han
Key Laboratory of Applied Technology on Green-Eco-Healthy Animal Husbandry of Zhejiang Province, College of Animal Science & Technology, College of Veterinary Medicine, Zhejiang A&F University, Hangzhou, P.R. China
Houhui Song
Key Laboratory of Applied Technology on Green-Eco-Healthy Animal Husbandry of Zhejiang Province, College of Animal Science & Technology, College of Veterinary Medicine, Zhejiang A&F University, Hangzhou, P.R. China
Yigang Xu
Key Laboratory of Applied Technology on Green-Eco-Healthy Animal Husbandry of Zhejiang Province, College of Animal Science & Technology, College of Veterinary Medicine, Zhejiang A&F University, Hangzhou, P.R. China
Bovine viral diarrhoea virus (BVDV) is the etiologic agent of bovine viral diarrhea-mucosal disease, one of the most important viral diseases in cattle, with inflammatory diarrhea, enteritis, and mucosa necrosis as the major clinical manifestations. NF-κB is an important transcription complex that regulates the expression of genes involved in inflammation and immune responses. NLRP3 inflammasome plays a key role in the development of inflammatory diseases. However, whether the activation of NF-κB is crucial for BVDV infection-induced inflammatory responses remains unclear. The results of our present study showed that BVDV infection significantly activated the NF-κB pathway and promoted the expression of NLRP3 inflammasome components (NLRP3, ASC, pro-caspase 1) as well inflammatory cytokine pro-IL-1β in BVDV-infected bovine cells, resulting in the cleavage of pro-caspase 1 and pro-IL-1β into active form caspase 1 and IL-1β. However, the levels of the NLRP3 inflammasome components and inflammatory cytokines were obviously inhibited, as well the cleavage of pro-caspase 1 and pro-IL-1β in the pre-treated bovine cells with NF-κB-specific inhibitors after BVDV infection. Further, cytopathic biotype BVDV (cpBVDV) Erns and NS5A proteins with their key functional domains contributed to BVDV-induced inflammatory responses via activating the NF-κB pathway were confirmed experimentally. Especially, the NS5A can promote cholesterol synthesis and accelerate its augmentation, further activating the NF-κB signalling pathway. Conclusively, our data elucidate that the activation of NF-κB signaling pathway plays a crucial role in cpBVDV infection-induced inflammatory responses.