SARS-CoV-2 Employ BSG/CD147 and ACE2 Receptors to Directly Infect Human Induced Pluripotent Stem Cell-Derived Kidney Podocytes.

Autor:	Kalejaiye TD; Department of Biomedical Engineering, Pratt School of Engineering, Duke University, Durham, NC, United States., Bhattacharya R; Department of Biomedical Engineering, Pratt School of Engineering, Duke University, Durham, NC, United States.; Center for Biomolecular and Tissue Engineering, Duke University, Durham, NC, United States., Burt MA; Department of Biomedical Engineering, Pratt School of Engineering, Duke University, Durham, NC, United States., Travieso T; Division of Infectious Diseases, Department of Medicine, Duke University School of Medicine, Durham, NC, United States.; Duke Human Vaccine Institute, Duke University Medical Center, Durham, NC, United States., Okafor AE; Department of Biomedical Engineering, Pratt School of Engineering, Duke University, Durham, NC, United States., Mou X; Department of Biomedical Engineering, Pratt School of Engineering, Duke University, Durham, NC, United States., Blasi M; Division of Infectious Diseases, Department of Medicine, Duke University School of Medicine, Durham, NC, United States.; Duke Human Vaccine Institute, Duke University Medical Center, Durham, NC, United States., Musah S; Department of Biomedical Engineering, Pratt School of Engineering, Duke University, Durham, NC, United States.; Center for Biomolecular and Tissue Engineering, Duke University, Durham, NC, United States.; Division of Nephrology, Department of Medicine, Duke University School of Medicine, Durham, NC, United States.; Developmental and Stem Cell Biology Program, Duke University, Durham, NC, United States.; Department of Cell Biology, Duke University, Durham, NC, United States.
Jazyk:	angličtina
Zdroj:	Frontiers in cell and developmental biology [Front Cell Dev Biol] 2022 Apr 20; Vol. 10, pp. 855340. Date of Electronic Publication: 2022 Apr 20 (Print Publication: 2022).
DOI:	10.3389/fcell.2022.855340
Abstrakt:	Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causes the Coronavirus disease 2019 (COVID-19), which has resulted in over 5.9 million deaths worldwide. While cells in the respiratory system are the initial target of SARS-CoV-2, there is mounting evidence that COVID-19 is a multi-organ disease. Still, the direct affinity of SARS-CoV-2 for cells in other organs such as the kidneys, which are often targeted in severe COVID-19, remains poorly understood. We employed a human induced pluripotent stem (iPS) cell-derived model to investigate the affinity of SARS-CoV-2 for kidney glomerular podocytes, and examined the expression of host factors for binding and processing of the virus. We studied cellular uptake of the live SARS-CoV-2 virus as well as a pseudotyped virus. Infection of podocytes with live SARS-CoV-2 or spike-pseudotyped lentiviral particles revealed cellular uptake even at low multiplicity of infection (MOI) of 0.01. We found that direct infection of human iPS cell-derived podocytes by SARS-CoV-2 virus can cause cell death and podocyte foot process retraction, a hallmark of podocytopathies and progressive glomerular diseases including collapsing glomerulopathy observed in patients with severe COVID-19 disease. We identified BSG/CD147 and ACE2 receptors as key mediators of spike binding activity in human iPS cell-derived podocytes. These results show that SARS-CoV-2 can infect kidney glomerular podocytes in vitro via multiple binding interactions and partners, which may underlie the high affinity of SARS-CoV-2 for kidney tissues. This stem cell-derived model is potentially useful for kidney-specific antiviral drug screening and mechanistic studies of COVID-19 organotropism. Competing Interests: SM is an inventor on a patent regarding podocyte differentiation. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. (Copyright © 2022 Kalejaiye, Bhattacharya, Burt, Travieso, Okafor, Mou, Blasi and Musah.)
Databáze:	MEDLINE
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