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

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Kalejaiye, Titilola D

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Bhattacharya, Rohan

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Burt, Morgan A

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Travieso, Tatianna

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Okafor, Arinze E

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Mou, Xingrui

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Blasi, Maria

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Musah, Samira

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2022-04-28T16:20:38Z

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2022-04-28T16:20:38Z

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2022-04-28T16:20:36Z

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<jats:p>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 <jats:italic>in vitro</jats:italic> 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.</jats:p>

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2296-634X

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https://hdl.handle.net/10161/24938

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Frontiers Media SA

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Frontiers in Cell and Developmental Biology

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10.3389/fcell.2022.855340

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

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Journal article

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Bhattacharya, Rohan|0000-0002-3663-9311

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Blasi, Maria|0000-0002-7091-0312

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Duke

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Pratt School of Engineering

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Student

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Biomedical Engineering

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Published online

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10

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