文献类型： 外文期刊

作者： Zhang, Shuai ¹ ; Zhang, Shuoshuo ¹ ; Hou, Yuchen ² ; Huang, Yanjie ¹ ; Cai, Jiajia ³ ; Wang, Guangzheng ¹ ; Cao, Yanan ¹ ; Chen, Zhenhai ² ; Fang, Xiaomin ⁴ ; Bao, Wenbin ¹ ;

作者机构： 1.Yangzhou Univ, Coll Anim Sci & Technol, Yangzhou, Peoples R China

2.Yangzhou Univ, Coll Vet Med, Yangzhou, Peoples R China

3.Yangzhou Univ, Joint Int Res Lab Agr & Agriprod Safety MOE, Yangzhou, Peoples R China

4.Jiangsu Acad Agr Sci, Inst Food Safety & Nutr, Nanjing, Peoples R China

关键词： Notch signaling pathway; PDCoV; goblet cells; intestinal organoids; intestinal stem cells

期刊名称：JOURNAL OF VIROLOGY （ 影响因子：5.4； 五年影响因子：4.9 ）

ISSN： 0022-538X

年卷期： 2023 年 97 卷 6 期

页码：

收录情况： SCI

摘要： The intestinal mucosal barrier, mainly secreted by the intestinal goblet cells, is a crucial first line of defense against pathogenic microorganisms. PDCoV regulates the function and differentiation of goblet cells, thereby disrupting the mucosal barrier; however, the mechanism by which PDCoV disrupts the barrier is not known. Goblet cells and their secreted mucus are important elements of the intestinal mucosal barrier, which allows host cells to resist invasion by intestinal pathogens. Porcine deltacoronavirus (PDCoV) is an emerging swine enteric virus that causes severe diarrhea in pigs and causes large economic losses to pork producers worldwide. To date, the molecular mechanisms by which PDCoV regulates the function and differentiation of goblet cells and disrupts the intestinal mucosal barrier remain to be determined. Here, we report that in newborn piglets, PDCoV infection disrupts the intestinal barrier: specifically, there is intestinal villus atrophy, crypt depth increases, and tight junctions are disrupted. There is also a significant reduction in the number of goblet cells and the expression of MUC-2. In vitro, using intestinal monolayer organoids, we found that PDCoV infection activates the Notch signaling pathway, resulting in upregulated expression of HES-1 and downregulated expression of ATOH-1 and thereby inhibiting the differentiation of intestinal stem cells into goblet cells. Our study shows that PDCoV infection activates the Notch signaling pathway to inhibit the differentiation of goblet cells and their mucus secretion, resulting in disruption of the intestinal mucosal barrier.IMPORTANCE The intestinal mucosal barrier, mainly secreted by the intestinal goblet cells, is a crucial first line of defense against pathogenic microorganisms. PDCoV regulates the function and differentiation of goblet cells, thereby disrupting the mucosal barrier; however, the mechanism by which PDCoV disrupts the barrier is not known. Here, we report that in vivo, PDCoV infection decreases villus length, increases crypt depth, and disrupts tight junctions. Moreover, PDCoV activates the Notch signaling pathway, inhibiting goblet cell differentiation and mucus secretion in vivo and in vitro. Thus, our results provide a novel insight into the mechanism underlying intestinal mucosal barrier dysfunction caused by coronavirus infection.