Transmissible gastroenteritis virus induces inflammatory responses via RIG-I/NF-&#954;B/HIF-1&#945;/glycolysis axis in intestinal organoids and <i>in vivo</i>.

Zhang, Yunhang; Yang, Ning; Li, Yang; Tan, Chen; Cai, Yifei; Rui, Xue; Liu, Yuanyuan; Fu, Yuguang; Liu, Guangliang

Transmissible gastroenteritis virus induces inflammatory responses via RIG-I/NF-κB/HIF-1α/glycolysis axis in intestinal organoids and in vivo.

Zhang, Yunhang; Yang, Ning; Li, Yang; Tan, Chen; Cai, Yifei; Rui, Xue; Liu, Yuanyuan; Fu, Yuguang; Liu, Guangliang.

Afiliación

Zhang Y; State Key Laboratory for Animal Disease Control and Prevention, College of Veterinary Medicine, Lanzhou University, Lanzhou Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Lanzhou, China.
Yang N; Molecular and Cellular Epigenetics (GIGA) and Molecular Biology (TERRA), University of Liege, Liege, Belgium.
Li Y; Hainan Key Laboratory of Tropical Animal Breeding and Infectious Disease Research, Institute of Animal Husbandry and Veterinary Medicine, Hainan Academy of Agricultural Sciences, Haikou, China.
Tan C; State Key Laboratory for Animal Disease Control and Prevention, College of Veterinary Medicine, Lanzhou University, Lanzhou Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Lanzhou, China.
Cai Y; Molecular and Cellular Epigenetics (GIGA) and Molecular Biology (TERRA), University of Liege, Liege, Belgium.
Rui X; Hainan Key Laboratory of Tropical Animal Breeding and Infectious Disease Research, Institute of Animal Husbandry and Veterinary Medicine, Hainan Academy of Agricultural Sciences, Haikou, China.
Liu Y; State Key Laboratory for Animal Disease Control and Prevention, College of Veterinary Medicine, Lanzhou University, Lanzhou Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Lanzhou, China.
Fu Y; Hainan Key Laboratory of Tropical Animal Breeding and Infectious Disease Research, Institute of Animal Husbandry and Veterinary Medicine, Hainan Academy of Agricultural Sciences, Haikou, China.
Liu G; State Key Laboratory for Animal Disease Control and Prevention, College of Veterinary Medicine, Lanzhou University, Lanzhou Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Lanzhou, China.

J Virol ; 98(6): e0046124, 2024 Jun 13.

Article en En | MEDLINE | ID: mdl-38780247

ABSTRACT

ABSTRACT

Transmissible gastroenteritis virus (TGEV)-induced enteritis is characterized by watery diarrhea, vomiting, and dehydration, and has high mortality in newborn piglets, resulting in significant economic losses in the pig industry worldwide. Conventional cell lines have been used for many years to investigate inflammation induced by TGEV, but these cell lines may not mimic the actual intestinal environment, making it difficult to obtain accurate results. In this study, apical-out porcine intestinal organoids were employed to study TEGV-induced inflammation. We found that apical-out organoids were susceptible to TGEV infection, and the expression of representative inflammatory cytokines was significantly upregulated upon TGEV infection. In addition, retinoic acid-inducible gene I (RIG-I) and the nuclear factor-kappa B (NF-κB) pathway were responsible for the expression of inflammatory cytokines induced by TGEV infection. We also discovered that the transcription factor hypoxia-inducible factor-1α (HIF-1α) positively regulated TGEV-induced inflammation by activating glycolysis in apical-out organoids, and pig experiments identified the same molecular mechanism as the ex vivo results. Collectively, we unveiled that the inflammatory responses induced by TGEV were modulated via the RIG-I/NF-κB/HIF-1α/glycolysis axis ex vivo and in vivo. This study provides novel insights into TGEV-induced enteritis and verifies intestinal organoids as a reliable model for investigating virus-induced inflammation. IMPORTANCE Intestinal organoids are a newly developed culture system for investigating immune responses to virus infection. This culture model better represents the physiological environment compared with well-established cell lines. In this study, we discovered that inflammatory responses induced by TGEV infection were regulated by the RIG-I/NF-κB/HIF-1α/glycolysis axis in apical-out porcine organoids and in pigs. Our findings contribute to understanding the mechanism of intestinal inflammation upon viral infection and highlight apical-out organoids as a physiological model to mimic virus-induced inflammation.

Asunto(s)

Gastroenteritis Porcina Transmisible; Glucólisis; Inflamación; Organoides; Virus de la Gastroenteritis Transmisible; Animales; Citocinas/metabolismo; Proteína 58 DEAD Box/metabolismo; Proteína 58 DEAD Box/genética; Gastroenteritis Porcina Transmisible/virología; Gastroenteritis Porcina Transmisible/metabolismo; Gastroenteritis Porcina Transmisible/patología; Subunidad alfa del Factor 1 Inducible por Hipoxia/metabolismo; Subunidad alfa del Factor 1 Inducible por Hipoxia/genética; Inflamación/metabolismo; Inflamación/virología; Intestinos/virología; Intestinos/patología; FN-kappa B/metabolismo; Organoides/virología; Organoides/metabolismo; Organoides/patología; Transducción de Señal; Porcinos; Virus de la Gastroenteritis Transmisible/fisiología

Palabras clave

HIF-1α; NF-κB; TGEV; apical-out intestinal organoids; inflammation

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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Organoides / Virus de la Gastroenteritis Transmisible / Gastroenteritis Porcina Transmisible / Glucólisis / Inflamación Límite: Animals Idioma: En Revista: J Virol Año: 2024 Tipo del documento: Article País de afiliación: China Pais de publicación: Estados Unidos

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