Deleterious effects of SARS-CoV-2 infection on human pancreatic cells
| Autor: | Gustavo Garcia, Dhruv Sareen, Yi Zhang, Wohaib Hasan, Yizhou Wang, Roberta de Souza Santos, Andrew R. Gross, Hanan Shaharuddin, Victoria Wang, Harneet Jawanda, Vaithilingaraja Arumugaswami |
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| Rok vydání: | 2021 |
| Předmět: |
0301 basic medicine
business.industry medicine.medical_treatment 030106 microbiology medicine.disease Virus Transcriptome 03 medical and health sciences 030104 developmental biology medicine.anatomical_structure Cytokine Immunology medicine Endocrine system Acute pancreatitis Pancreas business Receptor Respiratory tract |
| Popis: | SUMMARYCOVID-19 pandemic has infected more than 46 million people worldwide and caused more than 1.2 million deaths. It is transmitted by the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) and affects the respiratory tract as well as extra-pulmonary systems, including the pancreas, that express the virus entry receptor, Angiotensin-Converting Enzyme 2 (ACE2) receptor. Importantly, the endocrine and exocrine pancreas, the latter composed of ductal and acinar cells, express high levels of ACE2, which correlates to impaired functionality characterized as acute pancreatitis observed in some cases presenting with COVID-19. Since acute pancreatitis is already one of the most frequent gastrointestinal causes of hospitalization in the U.S. and the majority of studies investigating the effects of SARS-CoV-2 on the pancreas are clinical and observational, we utilized human iPSC technology to investigate the potential deleterious effects of SARS-CoV-2 infection on iPSC-derived pancreatic cultures containing endocrine and exocrine cells. Interestingly, SARS-CoV-2 is capable of infecting iPSC-derived pancreatic cells, thus perturbing their normal molecular and cellular phenotypes. The infection increased a key inflammatory cytokine, CXCL12, known to be involved in pancreas dysfunction. Transcriptome analysis of infected pancreatic cultures confirmed that SARS-CoV-2 hijacks the ribosomal machinery in these cells. Notably, the SARS-CoV-2 infectivity of the pancreas is confirmed in post-mortem tissues from COVID-19 patients, which showed co-localization of SARS-CoV-2 in pancreatic endocrine and exocrine cells and increased the expression of some pancreatic ductal stress response genes. Thus, we demonstrate for the first time that SARS-CoV-2 can directly infect human iPSC-derived pancreatic cells with supporting evidence of presence of the virus in post-mortem pancreatic tissue of confirmed COVID-19 human cases. This novel model of iPSC-derived pancreatic cultures will open new avenues for the comprehension of the SARS-CoV-2 infection and potentially establish a platform for endocrine and exocrine pancreas-specific antiviral drug screening. |
| Databáze: | OpenAIRE |
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