HIF-1α; In vivo; Intestinal organoid monolayer; TGEV; Type I and type III IFN production; Microbiology; Veterinary (all); General Veterinary; General Medicine
Abstract :
[en] Transmissible gastroenteritis virus (TGEV) is characterized by watery diarrhea, vomiting, and dehydration and is associated with high mortality especially in newborn piglets, causing significant economic losses to the global pig industry. Hypoxia inducible factor-1α (HIF-1α) has been identified as a key regulator of TGEV-induced inflammation, but understanding of the effect of HIF-1α on TGEV infection remains limited. This study found that TGEV infection was associated with a marked increase in HIF-1α expression in ST cells and an intestinal organoid epithelial monolayer. Furthermore, HIF-1α was shown to facilitate TGEV infection by targeting viral replication, which was achieved by restraining type I and type III interferon (IFN) production. In vivo experiments in piglets demonstrated that the HIF-1α inhibitor BAY87-2243 significantly reduced HIF-1α expression and inhibited TGEV replication and pathogenesis by activating IFN production. In summary, we unveiled that HIF-1α facilitates TGEV replication by restraining type I and type III IFN production in vitro, ex vivo, and in vivo. The findings from this study suggest that HIF-1α could be a novel antiviral target and candidate drug against TGEV infection.
Disciplines :
Veterinary medicine & animal health
Author, co-author :
Zhang, Yunhang ; Université de Liège - ULiège > TERRA Research Centre
Rui, Xue; State Key Laboratory for Animal Disease Control and Prevention, College of Veterinary Medicine, Lanzhou University, Lanzhou Veterinary Research Institute, Chinese Academy of Agricultural Sciences, China, Hainan Key Laboratory of Tropical Animal Breeding and Infectious Disease Research, Institute of Animal Husbandry and Veterinary Medicine, Hainan Academy of Agricultural Sciences, China, College of Veterinary Medicine, Xinjiang Agricultural University, China
Li, Yang; State Key Laboratory for Animal Disease Control and Prevention, College of Veterinary Medicine, Lanzhou University, Lanzhou Veterinary Research Institute, Chinese Academy of Agricultural Sciences, China
Zhang, Yue; State Key Laboratory for Animal Disease Control and Prevention, College of Veterinary Medicine, Lanzhou University, Lanzhou Veterinary Research Institute, Chinese Academy of Agricultural Sciences, China
Cai, Yifei; State Key Laboratory for Animal Disease Control and Prevention, College of Veterinary Medicine, Lanzhou University, Lanzhou Veterinary Research Institute, Chinese Academy of Agricultural Sciences, China, Hainan Key Laboratory of Tropical Animal Breeding and Infectious Disease Research, Institute of Animal Husbandry and Veterinary Medicine, Hainan Academy of Agricultural Sciences, China, Nutritional Biology, Wageningen University and Research, Wageningen, the Netherlands
Tan, Chen ; Université de Liège - ULiège > TERRA Research Centre
Yang, Ning; State Key Laboratory for Animal Disease Control and Prevention, College of Veterinary Medicine, Lanzhou University, Lanzhou Veterinary Research Institute, Chinese Academy of Agricultural Sciences, China, Molecular and Cellular Epigenetics (GIGA) and Molecular Biology (TERRA), University of Liege, Belgium, Hainan Key Laboratory of Tropical Animal Breeding and Infectious Disease Research, Institute of Animal Husbandry and Veterinary Medicine, Hainan Academy of Agricultural Sciences, China
Liu, Yuanyuan; State Key Laboratory for Animal Disease Control and Prevention, College of Veterinary Medicine, Lanzhou University, Lanzhou Veterinary Research Institute, Chinese Academy of Agricultural Sciences, China, Hainan Key Laboratory of Tropical Animal Breeding and Infectious Disease Research, Institute of Animal Husbandry and Veterinary Medicine, Hainan Academy of Agricultural Sciences, China, College of Veterinary Medicine, Xinjiang Agricultural University, China
Fu, Yuguang; State Key Laboratory for Animal Disease Control and Prevention, College of Veterinary Medicine, Lanzhou University, Lanzhou Veterinary Research Institute, Chinese Academy of Agricultural Sciences, China
Liu, Guangliang; State Key Laboratory for Animal Disease Control and Prevention, College of Veterinary Medicine, Lanzhou University, Lanzhou Veterinary Research Institute, Chinese Academy of Agricultural Sciences, China, Hainan Key Laboratory of Tropical Animal Breeding and Infectious Disease Research, Institute of Animal Husbandry and Veterinary Medicine, Hainan Academy of Agricultural Sciences, China, College of Veterinary Medicine, Xinjiang Agricultural University, China. Electronic address: LiuGuangliang01@caas.cn
Language :
English
Title :
Hypoxia inducible factor-1α facilitates transmissible gastroenteritis virus replication by inhibiting type I and type III interferon production.
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