Infection of intestinal cells by SARS-CoV2 and its effects on intestinal function

SARS-CoV2感染肠道细胞及其对肠道功能的影响

• 批准号: 458633287
• 负责人: Professor Dr. Hassan Y. Naim
• 金额: --
• 依托单位: Institut für Biochemie
• 依托单位国家: 德国
• 项目类别: Research Grants
• 财政年份: 2021
• 资助国家: 德国
• 起止时间: 2020-12-31 至 2021-12-31
• 项目状态: 已结题
• 来源: https://gepris.dfg.de/gepris/projekt/458633287?language=en
• 关键词: Infection; intestinal; cells; SARS; CoV2

Apart from the respiratory tract, SARS-CoV-2 affects also other organs and tissues. Among them, the intestinal tract plays a prominent role, because the virus may not only cause diarrhea, the released virus may in addition contribute to the transmission and spread of infection and/or it may serve as an indicator of infection. Here, we will utilize human intestinal Caco-2 cells to characterize the infection of differentiated intestinal epithelial cells by SARS-CoV-2. Different parameters of infection will be determined, such as amount of virus released, apical/basolateral virus entry and virus egress. Further, the cellular receptors implicated in virus transmission will be characterized. We will further investigate the trafficking and sorting of the cellular receptor(s), characterize their mode of interaction with membrane microdomains (lipid rafts) and assess the quality of this interaction via inhibitors of cholesterol and sphingolipids. The implication of glycosylation in the interaction between the spike protein and the cellular receptors will be envisaged using modulators of N- and O-linked glycosylation. Finally, the molecular basis for intestinal symptoms due to viral infection will be addressed by investigating the cell biology and physiology of crucial intestinal enzymes that are expressed in Caco-2 cells. Taken together, this project will provide valuable information about the infection of the intestinal epithelial cells by SARS-CoV-2 and help understand the importance of the intestinal infection relative to disease symptoms and the contribution of the intestine to virus transmission and to its role as an indicator of infection.

除了呼吸道，SARS-CoV-2还影响其他器官和组织。其中，肠道起着突出的作用，因为病毒不仅可能引起腹泻，释放的病毒还可能有助于感染的传播和扩散和/或它可以作为感染的指标。在这里，我们将利用人类肠道Caco-2细胞来表征SARS-CoV-2对分化的肠上皮细胞的感染。将确定不同的感染参数，例如释放的病毒量、顶侧/基底侧病毒进入和病毒排出。此外，将表征与病毒传播有关的细胞受体。我们将进一步研究细胞受体的运输和分选，表征它们与膜微区（脂筏）的相互作用模式，并通过胆固醇和鞘脂抑制剂评估这种相互作用的质量。使用N-和O-连接的糖基化的调节剂将设想刺突蛋白和细胞受体之间的相互作用中的糖基化的含义。最后，由于病毒感染引起的肠道症状的分子基础将通过研究Caco-2细胞中表达的关键肠道酶的细胞生物学和生理学来解决。总之，该项目将提供有关SARS-CoV-2感染肠道上皮细胞的有价值的信息，并有助于了解肠道感染相对于疾病症状的重要性，肠道对病毒传播的贡献及其作为感染指标的作用。