Tropism of SARS-CoV-2 for human cortical astrocytes.
Tropism of SARS-CoV-2 for human cortical astrocytes.
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DOI：
10.1073/pnas.2122236119
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发表时间：
2022-07-26
影响因子：
11.1
通讯作者：
中科院分区：
文献类型：
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作者：
多达三分之一的COVID-19患者或康复者会出现神经系统和神经精神症状。为了解决严重急性呼吸综合征冠状病毒2（SARS-CoV-2）的神经嗜性，我们评估了初级发育和成人皮质组织和干细胞衍生的皮质类器官对SARS-CoV-2感染的脆弱性。我们在人类皮质星形胶质细胞中观察到强大的感染和病毒复制;它们变得具有反应性，增加了生长因子信号传导，并激活细胞应激。尽管星形胶质细胞感染，但其他神经细胞类型（包括神经元）的感染很少。令人惊讶的是，我们发现星形胶质细胞感染不太可能由主要的冠状病毒受体ACE 2介导，而是观察到星形胶质细胞上表达的替代糖蛋白CD 147和DPP 4;它们是SARS-CoV-2感染所必需和充分的。严重急性呼吸综合征冠状病毒2（SARS-CoV-2）容易感染多种细胞类型，影响重要器官系统的功能，对呼吸功能的影响尤其严重。神经系统症状，其严重程度不等，伴随多达三分之一的COVID-19病例，表明神经细胞类型的潜在脆弱性。为了评估人类皮质细胞是否可以被SARS-CoV-2直接感染，我们利用了来自发育和成人阶段的干细胞衍生的皮质类器官以及原代人类皮质组织。我们发现在原代组织和类器官培养中，皮质星形胶质细胞的感染显著且占主导地位，其他皮质群体的感染最小。感染和旁观者星形胶质细胞在炎症基因表达、反应性特征、增加的细胞因子和生长因子信号传导以及细胞应激方面具有相应的增加。虽然人类皮质细胞，特别是星形胶质细胞，没有可观察到的ACE 2表达，但我们在感染的星形胶质细胞中发现了高水平的冠状病毒辅助受体，包括CD 147和DPP 4。降低辅助受体丰度和活性降低总体感染率，增加表达足以促进感染。因此，我们发现SARS-CoV-2对人类星形胶质细胞的嗜性导致依赖于冠状病毒辅助受体的炎性神经胶质样损伤。
Neurological and neuropsychiatric symptoms occur in as many as one-third of patients with or recovering from COVID-19. To address severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) neural tropism, we evaluated the vulnerability of primary developing and adult cortical tissue and stem-cell-derived cortical organoids to SARS-CoV-2 infection. We observe robust infection and viral replication in human cortical astrocytes; they become reactive, have increased growth factor signaling, and activate cellular stress. Despite infection in astroglial cells, there is minimal infection of other neural cell types, including neurons. Surprisingly, we discover that astrocyte infection is unlikely to be mediated by the predominant coronavirus receptor, ACE2, and instead observe alternative glycoproteins, CD147 and DPP4, expressed on astrocytes; they are necessary and sufficient for SARS-CoV-2 infection. The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) readily infects a variety of cell types impacting the function of vital organ systems, with particularly severe impact on respiratory function. Neurological symptoms, which range in severity, accompany as many as one-third of COVID-19 cases, indicating a potential vulnerability of neural cell types. To assess whether human cortical cells can be directly infected by SARS-CoV-2, we utilized stem-cell-derived cortical organoids as well as primary human cortical tissue, both from developmental and adult stages. We find significant and predominant infection in cortical astrocytes in both primary tissue and organoid cultures, with minimal infection of other cortical populations. Infected and bystander astrocytes have a corresponding increase in inflammatory gene expression, reactivity characteristics, increased cytokine and growth factor signaling, and cellular stress. Although human cortical cells, particularly astrocytes, have no observable ACE2 expression, we find high levels of coronavirus coreceptors in infected astrocytes, including CD147 and DPP4. Decreasing coreceptor abundance and activity reduces overall infection rate, and increasing expression is sufficient to promote infection. Thus, we find tropism of SARS-CoV-2 for human astrocytes resulting in inflammatory gliosis-type injury that is dependent on coronavirus coreceptors.
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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：
Daniloski Z;Jordan TX;Wessels HH;Hoagland DA;Kasela S;Legut M;Maniatis S;Mimitou EP;Lu L;Geller E;Danziger O;Rosenberg BR;Phatnani H;Smibert P;Lappalainen T;tenOever BR;Sanjana NE
通讯作者：
Sanjana NE
DOI：
10.1016/s1474-4422(20)30308-2
发表时间：
2020-11
期刊：
The Lancet. Neurology
影响因子：
--
作者：
Matschke J;Lütgehetmann M;Hagel C;Sperhake JP;Schröder AS;Edler C;Mushumba H;Fitzek A;Allweiss L;Dandri M;Dottermusch M;Heinemann A;Pfefferle S;Schwabenland M;Sumner Magruder D;Bonn S;Prinz M;Gerloff C;Püschel K;Krasemann S;Aepfelbacher M;Glatzel M
通讯作者：
Glatzel M
影响因子：
29
作者：
Bartley CM;Johns C;Ngo TT;Dandekar R;Loudermilk RL;Alvarenga BD;Hawes IA;Zamecnik CR;Zorn KC;Alexander JR;Wapniarski AE;DeRisi JL;Francisco C;Nash KB;Wietstock SO;Pleasure SJ;Wilson MR
通讯作者：
Wilson MR
影响因子：
8.3
作者：
Jin R;Xiao AY;Chen R;Granger DN;Li G
通讯作者：
Li G