SARS-CoV-2 Employ BSG/CD147 and ACE2 Receptors to Directly Infect Human Induced Pluripotent Stem Cell-Derived Kidney Podocytes.
SARS-CoV-2 Employ BSG/CD147 and ACE2 Receptors to Directly Infect Human Induced Pluripotent Stem Cell-Derived Kidney Podocytes.
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DOI：
10.3389/fcell.2022.855340
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发表时间：
2022
影响因子：
5.5
通讯作者：
Musah, Samira
中科院分区：
文献类型：
--
作者：
Kalejaiye, Titilola D.;Bhattacharya, Rohan;Burt, Morgan A.;Travieso, Tatianna;Okafor, Arinze E.;Mou, Xingrui;Blasi, Maria;Musah, Samira
关键词：
严重的急性呼吸道综合征冠状病毒2（SARS-COV-2）导致2019年冠状病毒病（Covid-19），导致全球590万人死亡。尽管呼吸系统中的细胞是SARS-COV-2的初始靶标，但有越来越多的证据表明Covid-19是一种多器官疾病。尽管如此，SARS-COV-2对其他器官（例如肾脏）的细胞的直接亲和力（通常是在严重的COVID-19中）仍然尚不清楚。我们采用了人类诱导的多能茎（IPS）细胞衍生的模型来研究SARS-COV-2对肾脏肾小球足细胞的亲和力，并检查了宿主因子的表达以表达病毒的结合和加工。我们研究了活SARS-COV-2病毒的细胞摄取以及伪型病毒。活体SARS-COV-2或尖峰型慢病毒颗粒感染足细胞，即使在低多种感染（MOI）为0.01的情况下，细胞摄取也会显示出细胞的摄取。我们发现，通过SARS-COV-2病毒直接感染人IPS细胞衍生的足细胞会导致细胞死亡和足细胞足过程缩回，这是足细胞病的标志和进行性肾小球疾病的标志，包括患有严重COVID 199疾病的患者观察到的肾小球病折叠。我们将BSG/CD147和ACE2受体确定为人IPS细胞衍生的足细胞中尖峰结合活性的关键介体。这些结果表明，SARS-COV-2可以通过多种结合相互作用和伴侣在体外感染肾肾小球足细胞，这可能是SARS-COV-2对肾脏组织的高亲和力。该干细胞衍生的模型可能可用于肾脏特异性抗病毒药筛查和COVID-19的机理研究。
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.
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DOI：
10.1126/science.1193032
发表时间：
2010-08-13
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Genovese G;Friedman DJ;Ross MD;Lecordier L;Uzureau P;Freedman BI;Bowden DW;Langefeld CD;Oleksyk TK;Uscinski Knob AL;Bernhardy AJ;Hicks PJ;Nelson GW;Vanhollebeke B;Winkler CA;Kopp JB;Pays E;Pollak MR
通讯作者：
Pollak MR
影响因子：
5.4
作者：
Glowacka, Ilona;Bertram, Stephanie;Poehlmann, Stefan
通讯作者：
Poehlmann, Stefan
影响因子：
--
作者：
de Wilde AH;Snijder EJ;Kikkert M;van Hemert MJ
通讯作者：
van Hemert MJ
人类肾脏是新型严重急性呼吸综合征冠状病毒2感染的目标
影响因子：
16.6
作者：
Diao B;Wang C;Wang R;Feng Z;Zhang J;Yang H;Tan Y;Wang H;Wang C;Liu L;Liu Y;Liu Y;Wang G;Yuan Z;Hou X;Ren L;Wu Y;Chen Y
通讯作者：
Chen Y
影响因子：
9.9
作者：
Hikmet, Feria;Mear, Loren;Lindskog, Cecilia
通讯作者：
Lindskog, Cecilia