SARS-CoV-2 infects and replicates in cells of the human endocrine and exocrine pancreas.
Aged
Aged, 80 and over
Angiotensin-Converting Enzyme 2
/ biosynthesis
COVID-19
/ physiopathology
Cells, Cultured
Diabetes Mellitus
Female
Humans
Islets of Langerhans
/ cytology
Male
Pancreas, Exocrine
/ cytology
Pancreatic Diseases
/ etiology
SARS-CoV-2
/ growth & development
Serine Endopeptidases
/ biosynthesis
Virus Internalization
Virus Replication
Journal
Nature metabolism
ISSN: 2522-5812
Titre abrégé: Nat Metab
Pays: Germany
ID NLM: 101736592
Informations de publication
Date de publication:
02 2021
02 2021
Historique:
received:
15
07
2020
accepted:
14
01
2021
pubmed:
5
2
2021
medline:
5
3
2021
entrez:
4
2
2021
Statut:
ppublish
Résumé
Infection-related diabetes can arise as a result of virus-associated β-cell destruction. Clinical data suggest that the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), causing the coronavirus disease 2019 (COVID-19), impairs glucose homoeostasis, but experimental evidence that SARS-CoV-2 can infect pancreatic tissue has been lacking. In the present study, we show that SARS-CoV-2 infects cells of the human exocrine and endocrine pancreas ex vivo and in vivo. We demonstrate that human β-cells express viral entry proteins, and SARS-CoV-2 infects and replicates in cultured human islets. Infection is associated with morphological, transcriptional and functional changes, including reduced numbers of insulin-secretory granules in β-cells and impaired glucose-stimulated insulin secretion. In COVID-19 full-body postmortem examinations, we detected SARS-CoV-2 nucleocapsid protein in pancreatic exocrine cells, and in cells that stain positive for the β-cell marker NKX6.1 and are in close proximity to the islets of Langerhans in all four patients investigated. Our data identify the human pancreas as a target of SARS-CoV-2 infection and suggest that β-cell infection could contribute to the metabolic dysregulation observed in patients with COVID-19.
Identifiants
pubmed: 33536639
doi: 10.1038/s42255-021-00347-1
pii: 10.1038/s42255-021-00347-1
doi:
Substances chimiques
ACE2 protein, human
EC 3.4.17.23
Angiotensin-Converting Enzyme 2
EC 3.4.17.23
Serine Endopeptidases
EC 3.4.21.-
TMPRSS2 protein, human
EC 3.4.21.-
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
149-165Subventions
Organisme : Baden-Württemberg Stiftung (Baden-Württemberg Foundation)
ID : ExPoChip
Organisme : Deutsche Forschungsgemeinschaft (German Research Foundation)
ID : 376202546
Organisme : Deutsche Forschungsgemeinschaft (German Research Foundation)
ID : GRK 2254/1
Organisme : Deutsche Forschungsgemeinschaft (German Research Foundation)
ID : CRC1279
Organisme : Deutsche Forschungsgemeinschaft (German Research Foundation)
ID : SPP1923
Organisme : Deutsche Forschungsgemeinschaft (German Research Foundation)
ID : "focus funding on COVID-19" DFG KL 2544/8-1 - AO 673221
Organisme : Deutsche Forschungsgemeinschaft (German Research Foundation)
ID : "Sachbeihilfe" KL 2544/7-1
Organisme : Deutsche Forschungsgemeinschaft (German Research Foundation)
ID : "Heisenberg-Programm" KL 2544/6-1
Organisme : Deutsche Forschungsgemeinschaft (German Research Foundation)
ID : K.L. 2544/1-1 and 1-2 and 5-1
Commentaires et corrections
Type : CommentIn
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