传染性胃肠炎病毒（TGEV）引起的肠炎以水样腹泻、呕吐和脱水为特征，新生仔猪死亡率高，给全球养猪业造成重大经济损失。传统细胞系多年来一直用于研究TGEV引起的炎症，但这些细胞系可能无法模拟实际的肠道环境，因此很难获得准确的结果。在这项研究中，采用顶端出的猪肠道类器官来研究 TEGV 诱导的炎症。我们发现顶端类器官对TGEV感染敏感，并且代表性炎症细胞因子的表达在TGEV感染后显着上调。此外，视黄酸诱导基因I (RIG-I)和核因子-κB (NF-κB)途径负责TGEV感染诱导的炎症细胞因子的表达。我们还发现，转录因子缺氧诱导因子-1α (HIF-1α) 通过激活顶端类器官中的糖酵解来正向调节 TGEV 诱导的炎症，猪实验也发现了与离体结果相同的分子机制。总的来说，我们揭示了 TGEV 诱导的炎症反应在体外和体内通过 RIG-I/NF-κB/HIF-1α/糖酵解轴进行调节。这项研究为TGEV引起的肠炎提供了新的见解，并验证了肠道类器官作为研究病毒引起的炎症的可靠模型。肠道类器官是一种新开发的培养系统，用于研究对病毒感染的免疫反应。与成熟的细胞系相比，这种培养模型更好地代表了生理环境。在这项研究中，我们发现在猪类器官和猪中，TGEV 感染诱导的炎症反应受到 RIG-I/NF-κB/HIF-1α/糖酵解轴的调节。我们的研究结果有助于理解病毒感染引起的肠道炎症机制，并强调顶端类器官作为模拟病毒引起的炎症的生理模型。

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.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.