SARS-CoV-2 leverages airway epithelial protective mechanism for viral infection.
SARS-CoV-2 leverages airway epithelial protective mechanism for viral infection.
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DOI：
10.1016/j.isci.2023.106175
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发表时间：
2023-03-17
期刊：
影响因子：
5.8
通讯作者：
Levchenko, Andre
中科院分区：
文献类型：
--
作者：
Greaney, Allison Marie;Raredon, Micha Sam Brickman;Kochugaeva, Maria P.;Niklason, Laura E.;Levchenko, Andre
尽管有许多共同努力，以更好地了解严重急性呼吸综合征冠状病毒2（SARS-CoV-2）病毒感染，相对较少的是知道的动态早期病毒进入和感染的气道。在这里，我们分析了早期SARS-CoV-2感染的人源化体外模型的单细胞RNA测序数据集，以阐明病毒触发支气管上皮细胞系统水平反应的关键机制。我们发现SARS-CoV-2病毒优先通过纤毛细胞前体进入组织，产生一群感染的成熟纤毛细胞，这些细胞向基底细胞发出信号，诱导进一步快速分化。在感染后三天干扰素信号传导开始之前，通过进一步的细胞-细胞通信来减轻感染的这种前馈回路。这些发现表明病毒劫持了潜在的有益组织修复机制，可能会加剧结果。这项工作阐明了屏障组织和病毒感染之间的相互作用，并可能提出针对非免疫反应机制的替代治疗方法。SARS-CoV-2感染的scRNA-seq显示病毒通过纤毛祖细胞进入感染第1天诱导分化时，基底细胞被耗尽感染的纤毛细胞主要通过TGFβ途径表达促分化信号病毒可以“劫持”组织修复机制，增加病毒载量生物科学;免疫学;病毒学;转录组学
Despite much concerted effort to better understand severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) viral infection, relatively little is known about the dynamics of early viral entry and infection in the airway. Here we analyzed a single-cell RNA sequencing dataset of early SARS-CoV-2 infection in a humanized in vitro model, to elucidate key mechanisms by which the virus triggers a cell-systems-level response in the bronchial epithelium. We find that SARS-CoV-2 virus preferentially enters the tissue via ciliated cell precursors, giving rise to a population of infected mature ciliated cells, which signal to basal cells, inducing further rapid differentiation. This feedforward loop of infection is mitigated by further cell-cell communication, before interferon signaling begins at three days post-infection. These findings suggest hijacking by the virus of potentially beneficial tissue repair mechanisms, possibly exacerbating the outcome. This work both elucidates the interplay between barrier tissues and viral infections and may suggest alternative therapeutic approaches targeting non-immune response mechanisms. scRNA-seq of initial SARS-CoV-2 infection reveals viral entry via ciliated progenitors Basal cells are depleted as they are induced to differentiate on day 1 of infection Infected ciliated cells express pro-differentiation signals mainly via TGFβ pathway The virus can “hijack” tissue repair mechanisms, increasing viral load Biological sciences; Immunology; Virology; Transcriptomics
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DOI：
10.1074/jbc.m508381200
发表时间：
2006-02-10
期刊：
The Journal of biological chemistry
影响因子：
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作者：
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通讯作者：
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