Institute for Stem Cell Research and Regenerative Medicine, Medical Faculty, Heinrich Heine University, Moorenstr.5, 40225, Düsseldorf, Germany.
Sci Rep. 2020 Dec 8;10(1):21415. doi: 10.1038/s41598-020-78402-2.
The COVID-19 pandemic resulting from the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) which emerged in December 2019 in Wuhan in China has placed immense burden on national economies and global health. At present neither vaccination nor therapies are available. Here, we performed a meta-analysis of RNA-sequencing data from three studies employing human lung epithelial cells. Of these one focused on lung epithelial cells infected with SARS-CoV-2. We aimed at identifying genes co-expressed with angiotensin I converting enzyme 2 (ACE2) the human cell entry receptor of SARS-CoV-2, and unveiled several genes correlated or inversely correlated with high significance, among the most significant of these was the transmembrane serine protease 4 (TMPRSS4). Serine proteases are known to be involved in the infection process by priming the virus spike protein. Pathway analysis revealed virus infection amongst the most significantly correlated pathways. Gene Ontologies revealed regulation of viral life cycle, immune responses, pro-inflammatory responses- several interleukins such as IL6, IL1, IL20 and IL33, IFI16 regulating the interferon response to a virus, chemo-attraction of macrophages, and cellular stress resulting from activated Reactive Oxygen Species. We believe that this dataset will aid in a better understanding of the molecular mechanism(s) underlying COVID-19.
由 2019 年 12 月在中国武汉出现的严重急性呼吸综合征冠状病毒 2(SARS-CoV-2)引起的 COVID-19 大流行,给各国经济和全球卫生带来了巨大负担。目前,既没有疫苗也没有治疗方法。在这里,我们对使用人肺上皮细胞的三项研究的 RNA 测序数据进行了荟萃分析。其中一项研究集中在感染 SARS-CoV-2 的肺上皮细胞上。我们旨在确定与 SARS-CoV-2 的人类细胞进入受体血管紧张素转换酶 2(ACE2)共表达的基因,并揭示了几个具有高度相关性或负相关性的基因,其中最重要的是跨膜丝氨酸蛋白酶 4(TMPRSS4)。丝氨酸蛋白酶已知参与病毒刺突蛋白的启动,从而参与感染过程。途径分析显示病毒感染是相关性最高的途径之一。基因本体论揭示了病毒生命周期、免疫反应、促炎反应的调节-几种白细胞介素,如 IL6、IL1、IL20 和 IL33,IFI16 调节对病毒的干扰素反应,巨噬细胞的趋化作用,以及由活性活性氧引起的细胞应激。我们相信,这个数据集将有助于更好地了解 COVID-19 背后的分子机制。