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转录组分析揭示了 SARS-CoV-2 感染人肺细胞的新机制。

Transcriptomic analysis reveals novel mechanisms of SARS-CoV-2 infection in human lung cells.

机构信息

Department of Pain Medicine and Shenzhen Municipal Key Laboratory for Pain Medicine, Shenzhen Nanshan People's Hospital, The 6th Affiliated Hospital of Shenzhen University Health Science Center, Shenzhen, China.

Jinan University, Guangzhou, China.

出版信息

Immun Inflamm Dis. 2020 Dec;8(4):753-762. doi: 10.1002/iid3.366. Epub 2020 Oct 30.

Abstract

BACKGROUND

Severe acute respiratory syndrome coronavirus clade 2 (SARS-CoV-2) is a single-stranded RNA virus responsible for the global pandemic of the coronavirus disease-2019 (COVID-19). To date, there are still no effective approaches for the prevention and treatment of COVID-19.

OBJECTIVE

The present study aims to explore the possible mechanisms of SARS-CoV-2 infection in human lung cells.

METHODS

Data interpretation was conducted by recruiting bioinformatics analysis, including Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathways analysis using downloaded data from the NCBI Gene Expression Omnibus database.

RESULTS

The present study demonstrated that SARS-CoV-2 infection induces the upregulation of 14 interferon-stimulated genes, indicative of immune, and interferon responses to the virus. Notably, genes for pyrimidine metabolism and steroid hormone biosynthesis are selectively enriched in human lung cells after SARS-CoV-2 infection, suggesting that altered pyrimidine metabolism and steroid biosynthesis are remarkable, and perhaps druggable features after SARS-CoV-2 infection. Besides, there is a strong positive correlation between viral ORF1ab, ORF6, and angiotensin-converting enzyme 2 (ACE2) expression in human lung cells, implying that ACE2 facilitates SARS-CoV-2 infection and replication in host cells probably through the induction of ORF1ab and ORF6.

摘要

背景

严重急性呼吸综合征冠状病毒 2 型(SARS-CoV-2)是一种单链 RNA 病毒,导致了 2019 年冠状病毒病(COVID-19)的全球大流行。迄今为止,仍然没有预防和治疗 COVID-19 的有效方法。

目的

本研究旨在探索 SARS-CoV-2 感染人肺细胞的可能机制。

方法

通过招募生物信息学分析,包括基因本体论和京都基因与基因组百科全书途径分析,对从 NCBI Gene Expression Omnibus 数据库下载的数据进行解释。

结果

本研究表明,SARS-CoV-2 感染诱导 14 种干扰素刺激基因上调,表明对病毒的免疫和干扰素反应。值得注意的是,SARS-CoV-2 感染后,人类肺细胞中嘧啶代谢和类固醇激素生物合成的基因选择性富集,表明嘧啶代谢和类固醇生物合成的改变是 SARS-CoV-2 感染后的显著特征,且可能是可药物治疗的特征。此外,在人类肺细胞中,病毒 ORF1ab、ORF6 和血管紧张素转换酶 2(ACE2)的表达之间存在强烈的正相关,这表明 ACE2 通过诱导 ORF1ab 和 ORF6 促进 SARS-CoV-2 在宿主细胞中的感染和复制。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a3f5/7654422/324fd0a41527/IID3-8-753-g001.jpg

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