1. SARS-CoV-2 infects an in vitro model of the human developing pancreas through endocytosis
- Author
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Wojciech J. Szlachcic, Agnieszka Dabrowska, Aleksandra Milewska, Natalia Ziojla, Katarzyna Blaszczyk, Emilia Barreto-Duran, Marek Sanak, Marcin Surmiak, Katarzyna Owczarek, Dariusz Grzanka, Julia Durzynska, Krzysztof Pyrc, and Malgorzata Borowiak
- Subjects
Model organism ,Virology ,Science - Abstract
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.
- Published
- 2022
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