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《BioRxiv，4月10日，Type 2 and interferon inflammation strongly regulate SARS-CoV-2 related gene expression in the airway epithelium》

  • 来源专题：COVID-19科研动态监测
  • 编译者： zhangmin
  • 发布时间：2020-04-29

  • Type 2 and interferon inflammation strongly regulate SARS-CoV-2 related gene expression in the airway epithelium

    Satria P. Sajuthi, Peter DeFord, Nathan D. Jackson, Michael T. Montgomery, Jamie L. Everman, Cydney L. Rios, Elmar Pruesse, James D. Nolin, Elizabeth G. Plender, Michael E. Wechsler, Angel CY Mak, Celeste Eng, Sandra Salazar, Vivian Medina, Eric M. Wohlford, Scott Huntsman, Deborah A. Nickerson, Soren Germer, Michael C. Zody, Gonçalo Abecasis, Hyun Min Kang, Kenneth M. Rice, Rajesh Kumar, Sam Oh, Jose Rodriguez-Santana, Esteban G. Burchard, Max A. Seibold

    doi: https://doi.org/10.1101/2020.04.09.034454

    Abstract

    Coronavirus disease 2019 (COVID-19) outcomes vary from asymptomatic infection to death. This disparity may reflect different airway levels of the SARS-CoV-2 receptor, ACE2, and the spike protein activator, TMPRSS2. Here we explore the role of genetics and co-expression networks in regulating these genes in the airway, through the analysis of nasal airway transcriptome data from 695 children. We identify expression quantitative trait loci (eQTL) for both ACE2 and TMPRSS2, that vary in frequency across world populations. Importantly, we find TMPRSS2 is part of a mucus secretory network, highly upregulated by T2 inflammation through the action of interleukin-13, and that interferon response to respiratory viruses highly upregulates ACE2 expression. Finally, we define airway responses to coronavirus infections in children, finding that these infections upregulate IL6 while also stimulating a more pronounced cytotoxic immune response relative to other respiratory viruses. Our results reveal mechanisms likely influencing SARS-CoV-2 infectivity and COVID-19 clinical outcomes.

    *注，本文为预印本论文手稿，是未经同行评审的初步报告，其观点仅供科研同行交流，并不是结论性内容，请使用者谨慎使用.

  • 原文来源：https://www.biorxiv.org/content/10.1101/2020.04.09.034454v1
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  • 《4月10日_2型细胞因子驱动的炎症和干扰素显著影响气道上皮细胞中SARS-CoV-2相关基因的表达》
    • 来源专题：COVID-19科研动态监测
    • 编译者：xuwenwhlib
    • 发布时间：2020-04-29
    • 信息名称：2型细胞因子驱动的炎症和干扰素显著影响气道上皮细胞中SARS-CoV-2相关基因的表达 1.时间：2020年4月10日 2.机构或团队：美国国立犹太健康中心、加州大学旧金山分校、华盛顿大学、布罗特曼•巴蒂精密医学研究所、纽约基因组研究中心、密歇根大学、美国西北大学、科罗拉多大学 3.事件概要： 4月28日，Nature Reviews Immunology发文分析了美国国立犹太健康中心等于4月10日在bioRxiv上发表的题为“Type 2 and interferon inflammation strongly regulate SARS-CoV-2 related gene expression in the airway epithelium”的文章。文章指出，COVID-19的结果从无症状感染到死亡各不相同，这种差异性可能反映了人体气道上皮细胞中SARS-CoV-2受体ACE2和刺突蛋白激活剂TMPRSS2表达水平的不同。文章中，研究人员通过分析695名儿童的鼻气道转录组数据，探讨基因和共表达网络在调节气道上皮细胞中这些基因表达的作用。研究确定了ACE2和TMPRSS2的表达数量性状位点（eQTL），发现其在不同人群中的出现频率不同。研究还发现TMPRSS2是粘液分泌网络的一部分，白细胞介素-13可高度上调2型细胞因子驱动的炎症，干扰素对呼吸道病毒的反应高度上调ACE2的表达。最后，作者定义了儿童冠状病毒感染的气道反应，发现这些感染上调了IL6，同时也刺激了相对于其他呼吸道病毒更明显的细胞毒性免疫反应。作者指出，这些研究结果揭示了可能影响SARS-CoV-2感染性和COVID-19临床结果的机制。 *注，本文为预印本论文手稿，是未经同行评审的初步报告，其观点仅供科研同行交流，并不是结论性内容，请使用者谨慎使用。 4.附件： 原文链接： https://www.biorxiv.org/content/10.1101/2020.04.09.034454v1
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  • 《Cell，4月21日，SARS-CoV-2 receptor ACE2 is an interferon-stimulated gene in human airway epithelial cells and is detected in specific cell subsets across tissues》
    • 来源专题：COVID-19科研动态监测
    • 编译者：zhangmin
    • 发布时间：2020-04-23
    • Summary There is pressing urgency to understand the pathogenesis of the severe acute respiratory syndrome coronavirus clade 2 (SARS-CoV-2) which causes the disease COVID-19. SARS-CoV2 spike (S)-protein binds ACE2, and in concert with host proteases, principally TMPRSS2, promotes cellular entry. The cell subsets targeted by SARS-CoV-2 in host tissues, and the factors that regulate ACE2 expression, remain unknown. Here, we leverage human, non-human primate, and mouse single-cell RNA-sequencing (scRNA-seq) datasets across health and disease to uncover putative targets of SARS-CoV-2 amongst tissue-resident cell subsets. We identify ACE2 and TMPRSS2 co-expressing cells within lung type II pneumocytes, ileal absorptive enterocytes, and nasal goblet secretory cells. Strikingly, we discover that ACE2 is a human interferonstimulated gene (ISG) in vitro using airway epithelial cells, and extend our findings to in vivo viral infections. Our data suggest that SARS-CoV-2 could exploit species-specific interferon-driven upregulation of ACE2, a tissue-protective mediator during lung injury, to enhance infection.
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