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  • 标题:SARS-CoV-2 infects an in vitro model of the human developing pancreas through endocytosis
  • 本地全文:下载
  • 作者:Wojciech J. Szlachcic ; Agnieszka Dabrowska ; Aleksandra Milewska
  • 期刊名称:iScience
  • 印刷版ISSN:2589-0042
  • 出版年度:2022
  • 卷号:25
  • 期号:7
  • 页码:1-22
  • DOI:10.1016/j.isci.2022.104594
  • 语种:English
  • 出版社:Elsevier
  • 摘要:SummaryRecent 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 progenitorsin 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.Graphical abstractDisplay OmittedHighlights•SARS-CoV-2 receptors are present in human developing pancreasin vivoandin vitro•SARS-CoV-2 infects multipotent and endocrine pancreatic progenitorsin vitro•SARS-CoV-2 enters the progenitors via alternate cathepsin-mediated endocytosisModel organism; Virology
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