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SARS-CoV-2 infects human pancreatic β cells and elicits β cell impairment

2021; Cell Press; Volume: 33; Issue: 8 Linguagem: Inglês

10.1016/j.cmet.2021.05.013

1932-7420

Chien-Ting Wu, Peter V. Lidsky, Yinghong Xiao, Ivan T. Lee, Ran Cheng, Tsuguhisa Nakayama, Sizun Jiang, János Demeter, Romina J. Bevacqua, Charles Chang, Robert L. Whitener, Anna K. Stalder, Bokai Zhu, Han Chen, Yury Goltsev, Alexandar Tzankov, Jayakar V. Nayak, Garry P. Nolan, Matthias S. Matter, Raul Andino, Peter K. Jackson,

Diabetes and associated disorders

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.