SARS-CoV-2 Employ BSG/CD147 and ACE2 Receptors to Directly Infect Human Induced Pluripotent Stem Cell-Derived Kidney Podocytes
dc.contributor.author | Kalejaiye, Titilola D | |
dc.contributor.author | Bhattacharya, Rohan | |
dc.contributor.author | Burt, Morgan A | |
dc.contributor.author | Travieso, Tatianna | |
dc.contributor.author | Okafor, Arinze E | |
dc.contributor.author | Mou, Xingrui | |
dc.contributor.author | Blasi, Maria | |
dc.contributor.author | Musah, Samira | |
dc.date.accessioned | 2022-04-28T16:20:38Z | |
dc.date.available | 2022-04-28T16:20:38Z | |
dc.date.updated | 2022-04-28T16:20:36Z | |
dc.description.abstract | <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> | |
dc.identifier.issn | 2296-634X | |
dc.identifier.uri | ||
dc.publisher | Frontiers Media SA | |
dc.relation.ispartof | Frontiers in Cell and Developmental Biology | |
dc.relation.isversionof | 10.3389/fcell.2022.855340 | |
dc.title | SARS-CoV-2 Employ BSG/CD147 and ACE2 Receptors to Directly Infect Human Induced Pluripotent Stem Cell-Derived Kidney Podocytes | |
dc.type | Journal article | |
duke.contributor.orcid | Bhattacharya, Rohan|0000-0002-3663-9311 | |
duke.contributor.orcid | Blasi, Maria|0000-0002-7091-0312 | |
pubs.organisational-group | Duke | |
pubs.organisational-group | Pratt School of Engineering | |
pubs.organisational-group | Student | |
pubs.organisational-group | Biomedical Engineering | |
pubs.publication-status | Published online | |
pubs.volume | 10 |
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