兰州兽医研究所刘光亮研究员团队在国际顶级期刊《Journal of Virology》上发表了题为“Transmissible gastroenteritis virus induces inflammatory responses via RIG-I/NF-κB/HIF-1α/glycolysis axis in intestinal organoids and in vivo”的研究论文，该研究旨在使用极性反转猪肠道类器官以及猪体内实验来研究传染性胃肠炎病毒（TGEV）引起的炎症反应，探索TGEV感染后的炎症反应机制。
TGEV对全球养猪业造成的重大经济损失，其感染引起的胃肠炎导致新生仔猪的高死亡率。传统细胞系虽被用于研究TGEV引起的炎症反应，但可能无法准确模拟实际肠道环境，导致难以获得准确的研究结果。肠道类器官是从Lgr5+干细胞分化而来，包含多种肠道细胞类型，更能代表肠道的生理环境，为研究病毒-宿主相互作用提供了一个更符合生理学特性的模型。
本研究首次采用极性反转猪肠道类器官和猪模型来探索TGEV诱导的炎症，并揭示了TGEV通过RIG-I/NF-κB/HIF-1α/糖酵解轴诱导炎症反应。研究结果不仅有助于理解TGEV感染引起的肠道炎症的机制，还突出了极性反转猪肠道类器官作为模拟病毒诱导的炎症生理模型的重要性。
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.
论文链接：https://journals.asm.org/doi/full/10.1128/jvi.00461-24?af=R
本期来源：中国动物保健
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