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

• Applicant: Professor Dr. Hassan Y. Naim
• Subject Area: Virology ; Biochemistry ; Gastroenterology ; Cell Biology
• Term: from 2021 to 2022
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 458633287

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.

• DFG Programme: Research Grants