脏器官在ACE2-依赖的SARS-CoV-2感染期间显示病毒进入途径的冗余性
Jessica M Vanslambrouck1,2, Jessica A Neil3, Rajeev Rudraraju3
1The Novo Nordisk Foundation Centre for Stem Cell Medicine (reNEW), Murdoch Children's Research Institute, Melbourne, Australia.
Journal of virology
|February 9, 2024
概括
这项研究表明,SARS-CoV-2主要通过ACE2通过双重处理途径感染脏近道管细胞. 像利西诺普利尔这样的常见血压药物不会增加细胞对COVID-19感染的易感性.
科学领域:
- 腎臟病學 (nephrology) 是一種醫學專業.
- 病毒学 病毒学
- 细胞生物学 细胞生物学
背景情况:
- COVID-19 患者经常经历急性损伤,促使对 SARS-CoV-2 直接向脏的调查.
- 以前使用脏器官的研究表明,SARS-CoV-2感染了近道管细胞,但器官不成熟性限制了对病毒途径和药物效应的理解.
- 在细胞中SARS-CoV-2进入和处理的精确机制以及抗高血压药物的影响仍然不清楚.
研究的目的:
- 为了阐明SARS-CoV-2进入人类细胞的机制,使用一种新的,成熟的近接管体有机体模型.
- 确定SARS-CoV-2在结合细胞中的ACE2受体后利用的病毒处理途径.
- 评估ACE抑制剂利西诺普里尔对脏细胞易受SARS-CoV-2感染的影响.
主要方法:
- 开发和使用人类诱导多能干细胞 (iPSC) 衍生器官,增强近接管道 (PT) 成熟度.
- 采用基因和药物介导的抑制来研究病毒的进入和处理因素.
- 将SARS-CoV-2注射到有机体中,并用lisinopril治疗以评估感染易感性.
主要成果:
- 证实ACE2是SARS-CoV-2进入细胞的必要受体.
- 确定了双重的病毒处理途径:一个涉及TMPRSS10的非内体途径和一个涉及Cathepsins (CTSL/CTSB) 的内细胞途径.
- 证明利西诺普里尔治疗对ACE2表达或脏器官中的SARS-CoV-2感染率没有显著影响.
结论:
- 这项研究提供了SARS-CoV-2进入成熟人类器官的第一个详细表征.
- 这些发现澄清了ACE2和下游处理途径在脏SARS-CoV-2感染中的作用.
- 研究表明,Lisinopril等ACE抑制剂不会增加脏细胞对SARS-CoV-2的脆弱性.
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