数字农科院2.0

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

文献类型： 外文期刊

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

作者机构：

关键词： TGEV;apical-out intestinal organoids;inflammation;NF-kappa B;HIF-1 alpha

期刊名称： JOURNAL OF VIROLOGY

ISSN： 0022-538X

年卷期： 2024 年

页码：

收录情况： SCIE（2024版）

摘要： 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-kappa B) pathway were responsible for the expression of inflammatory cytokines induced by TGEV infection. We also discovered that the transcription factor hypoxia-inducible factor-1 alpha (HIF-1 alpha) 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-kappa B/HIF-1 alpha/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.

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