Host metabolism dysregulation and cell tropism identification in human airway and alveolar organoids upon SARS-CoV-2 infection.
Host metabolism dysregulation and cell tropism identification in human airway and alveolar organoids upon SARS-CoV-2 infection.
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SARS-CoV-2感染后人体气道和肺泡类器官的宿主代谢失调和细胞向性识别
DOI：
10.1007/s13238-020-00811-w
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发表时间：
2021-09
期刊：
影响因子：
21.1
通讯作者：
Chen X
中科院分区：
文献类型：
--
作者：
Pei R;Feng J;Zhang Y;Sun H;Li L;Yang X;He J;Xiao S;Xiong J;Lin Y;Wen K;Zhou H;Chen J;Rong Z;Chen X
2019 年冠状病毒病 (COVID-19) 大流行是由严重急性呼吸综合征冠状病毒 2 (SARS-CoV-2) 感染引起，该病毒主要通过呼吸道飞沫传播并感染肺部。目前广泛使用的细胞系和动物由于细胞系（转化细胞或癌细胞）的异常状态以及动物和人类之间的物种差异而无法准确模拟人类的生理条件。类器官是干细胞衍生的自组织体外三维培养物，模拟自然器官的生理条件。在这里，我们发现 SARS-CoV-2 在人胚胎干细胞 (hESC) 衍生的肺类器官中感染并广泛复制，包括气道和肺泡类器官，涵盖了 SARS-CoV-2 在肺内的完整感染和传播途径。感染细胞为纤毛细胞、棒状细胞和肺泡2型(AT2)细胞，它们分别从近端到远端气道和终末肺泡依次定位。此外，RNA-seq揭示了细胞对病毒感染的早期反应，除了众所周知的免疫反应上调之外，还包括代谢过程的意外下调，尤其是脂质代谢。此外，瑞德西韦和人类中和抗体可有效抑制肺类器官中的 SARS-CoV-2 复制。因此，人肺类器官可以作为病理生理学模型来研究 SARS-CoV-2 感染的潜在机制，并发现和测试 COVID-19 的治疗药物。
The coronavirus disease 2019 (COVID-19) pandemic is caused by infection with the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which is spread primary via respiratory droplets and infects the lungs. Currently widely used cell lines and animals are unable to accurately mimic human physiological conditions because of the abnormal status of cell lines (transformed or cancer cells) and species differences between animals and humans. Organoids are stem cell-derived self-organized three-dimensional culturein vitroand model the physiological conditions of natural organs. Here we showed that SARS-CoV-2 infected and extensively replicated in human embryonic stem cells (hESCs)-derived lung organoids, including airway and alveolar organoids which covered the complete infection and spread route for SARS-CoV-2 within lungs. The infected cells were ciliated, club, and alveolar type 2 (AT2) cells, which were sequentially located from the proximal to the distal airway and terminal alveoli, respectively. Additionally, RNA-seq revealed early cell response to virus infection including an unexpected downregulation of the metabolic processes, especially lipid metabolism, in addition to the well-known upregulation of immune response. Further, Remdesivir and a human neutralizing antibody potently inhibited SARS-CoV-2 replication in lung organoids. Therefore, human lung organoids can serve as a pathophysiological model to investigate the underlying mechanism of SARS-CoV-2 infection and to discover and test therapeutic drugs for COVID-19.
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DOI：
10.1126/science.abd3072
发表时间：
2020-11-13
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Daly JL;Simonetti B;Klein K;Chen KE;Williamson MK;Antón-Plágaro C;Shoemark DK;Simón-Gracia L;Bauer M;Hollandi R;Greber UF;Horvath P;Sessions RB;Helenius A;Hiscox JA;Teesalu T;Matthews DA;Davidson AD;Collins BM;Cullen PJ;Yamauchi Y
通讯作者：
Yamauchi Y
影响因子：
64.5
作者：
Hou, Yixuan J.;Okuda, Kenichi;Baric, Ralph S.
通讯作者：
Baric, Ralph S.
影响因子：
5.4
作者：
Heurich, Adeline;Hofmann-Winkler, Heike;Poehlmann, Stefan
通讯作者：
Poehlmann, Stefan
影响因子：
5.4
作者：
Glowacka, Ilona;Bertram, Stephanie;Poehlmann, Stefan
通讯作者：
Poehlmann, Stefan
影响因子：
6.1
作者：
Banu N;Panikar SS;Leal LR;Leal AR
通讯作者：
Leal AR