Post by Nadica (She/Her) on Oct 31, 2024 3:55:08 GMT
SARS-CoV-2 infects human pancreatic β cells and elicits β cell impairment - Published Aug 3, 2021
Highlights
• SARS-CoV-2 infects β cells in COVID-19 patients and human islets in vitro
• SARS-CoV-2 infection causes β cell death and reduced GSIS in vitro
• Phosphoproteomics shows SARS-CoV-2 spike protein and virus induce apoptotic kinases
• High neuropilin-1 levels support β cell selectivity, and inhibitors block infection
Summary
Emerging evidence points toward an intricate relationship between the pandemic of coronavirus disease 2019 (COVID-19) and diabetes. While preexisting diabetes is associated with severe COVID-19, it is unclear whether COVID-19 severity is a cause or consequence of diabetes. To mechanistically link COVID-19 to diabetes, we tested whether insulin-producing pancreatic β cells can be infected by SARS-CoV-2 and cause β cell depletion. We found that the SARS-CoV-2 receptor, ACE2, and related entry factors (TMPRSS2, NRP1, and TRFC) are expressed in β cells, with selectively high expression of NRP1. We discovered that SARS-CoV-2 infects human pancreatic β cells in patients who succumbed to COVID-19 and selectively infects human islet β cells in vitro. We demonstrated that SARS-CoV-2 infection attenuates pancreatic insulin levels and secretion and induces β cell apoptosis, each rescued by NRP1 inhibition. Phosphoproteomic pathway analysis of infected islets indicates apoptotic β cell signaling, similar to that observed in type 1 diabetes (T1D). In summary, our study shows SARS-CoV-2 can directly induce β cell killing.
Graphical abstract
Highlights
• SARS-CoV-2 infects β cells in COVID-19 patients and human islets in vitro
• SARS-CoV-2 infection causes β cell death and reduced GSIS in vitro
• Phosphoproteomics shows SARS-CoV-2 spike protein and virus induce apoptotic kinases
• High neuropilin-1 levels support β cell selectivity, and inhibitors block infection
Summary
Emerging evidence points toward an intricate relationship between the pandemic of coronavirus disease 2019 (COVID-19) and diabetes. While preexisting diabetes is associated with severe COVID-19, it is unclear whether COVID-19 severity is a cause or consequence of diabetes. To mechanistically link COVID-19 to diabetes, we tested whether insulin-producing pancreatic β cells can be infected by SARS-CoV-2 and cause β cell depletion. We found that the SARS-CoV-2 receptor, ACE2, and related entry factors (TMPRSS2, NRP1, and TRFC) are expressed in β cells, with selectively high expression of NRP1. We discovered that SARS-CoV-2 infects human pancreatic β cells in patients who succumbed to COVID-19 and selectively infects human islet β cells in vitro. We demonstrated that SARS-CoV-2 infection attenuates pancreatic insulin levels and secretion and induces β cell apoptosis, each rescued by NRP1 inhibition. Phosphoproteomic pathway analysis of infected islets indicates apoptotic β cell signaling, similar to that observed in type 1 diabetes (T1D). In summary, our study shows SARS-CoV-2 can directly induce β cell killing.
Graphical abstract