SARS-CoV-2 infects an in vitro model of the human developing pancreas through endocytosis

iScience

Aleksandra Milewska¹  Julia Durzynska²  Marcin Surmiak³  Katarzyna Owczarek³  Krzysztof Pyrc⁴  Katarzyna Blaszczyk⁵  Wojciech J. Szlachcic⁵  Emilia Barreto-Duran⁵  Agnieszka Dabrowska⁶  Natalia Ziojla⁶  Dariusz Grzanka⁶  Marek Sanak⁶  Malgorzata Borowiak⁶ 

[1] Microbiology Department, Faculty of Biochemistry, Biophysics and Biotechnology, Jagiellonian University, Gronostajowa 7, 30-387 Krakow, Poland;Department of Clinical Pathomorphology, Faculty of Medicine, Collegium Medicum in Bydgoszcz, Nicolaus Copernicus University in Torun, 85-094 Bydgoszcz, Poland;Department of Internal Medicine, Faculty of Medicine, Jagiellonian University Medical College, 30-688 Kraków, Poland;Institute of Experimental Biology, Faculty of Biology, Adam Mickiewicz University, Uniwersytetu Poznanskiego 6, 61-614 Poznan, Poland;Institute of Molecular Biology and Biotechnology, Faculty of Biology, Adam Mickiewicz University, Uniwersytetu Poznanskiego 6, 61-614 Poznan, Poland;Malopolska Centre of Biotechnology, Jagiellonian University, Gronostajowa 7A, 30-387 Krakow, Poland;

关键词: Model organism;    Virology;   

DOI  :  

来源: DOAJ

【 摘 要 】

Summary: Recent studies showed that SARS-CoV-2 can infect adult human pancreas and trigger pancreatic damage. Here, using human fetal pancreas samples and 3D differentiation of human pluripotent cells into pancreatic endocrine cells, we determined that SARS-CoV-2 receptors ACE2, TMPRSS2, and NRP1 are expressed in precursors of insulin-producing pancreatic β-cells, rendering them permissive to SARS-CoV-2 infection. We also show that SARS-CoV-2 enters and undergoes efficient replication in human multipotent pancreatic and endocrine progenitors in vitro. Moreover, we investigated mechanisms by which SARS-CoV-2 enters pancreatic cells, and found that ACE2 mediates the entry, while NRP1 and TMPRSS2 do not. Surprisingly, we found that in pancreatic progenitors, SARS-CoV-2 enters cells via cathepsin-dependent endocytosis, which is a different route than in respiratory tract. Therefore, pancreatic spheroids might serve as a model to study candidate drugs for endocytosis-mediated viral entry inhibition and to investigate whether SARS-CoV-2 infection may affect pancreas development, possibly causing lifelong health consequences.

【 授权许可】

Unknown