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严重急性呼吸综合征冠状病毒2（SARS-CoV-2）编码的微小RNA参与病毒感染和宿主免疫反应过程。

SARS-CoV-2 encoded microRNAs are involved in the process of virus infection and host immune response.

作者信息

Liu Zhi, Wang Jianwei, Ge Yiyue, Xu Yuyu, Guo Mengchen, Mi Kai, Xu Rui, Pei Yang, Zhang Qiankun, Luan Xiaoting, Hu Zhibin, Chi Ying, Liu Xingyin

机构信息

State Key Laboratory of Reproductive Medicine, Center of Global Health, Nanjing Medical University, Nanjing, Jiangsu 211166, China.

Department of Pathogen Biology-Microbiology Division, Key Laboratory of Pathogen of Jiangsu Province, School of Basic Medical Science, Nanjing Medical University, Nanjing, Jiangsu 211166, China.

出版信息

J Biomed Res. 2021 Jan 29;35(3):216-227. doi: 10.7555/JBR.35.20200154.

DOI:10.7555/JBR.35.20200154
PMID:33963094
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC8193712/
Abstract

The outbreak of COVID-19 caused by SARS-CoV-2 is spreading worldwide, with the pathogenesis mostly unclear. Both virus and host-derived microRNA (miRNA) play essential roles in the pathology of virus infection. This study aims to uncover the mechanism for SARS-CoV-2 pathogenicity from the perspective of miRNA. We scanned the SARS-CoV-2 genome for putative miRNA genes and miRNA targets and conducted experiments to validate the virus-encoded miRNAs and their regulatory role on the putative targets. One of such virus-encoded miRNAs, MR147-3p, was overexpressed that resulted in significantly decreased transcript levels of all of the predicted targets in human, , , , and in the virus-infected cells. The analysis showed that the immune response and cytoskeleton organization are two of the most notable biological processes regulated by the infection-modulated miRNAs. Additionally, the genomic mutation of SARS-CoV-2 contributed to the changed miRNA repository and targets, suggesting a possible role of miRNAs in the attenuated phenotype of SARS-CoV-2 during its evolution. This study provided a comprehensive view of the miRNA-involved regulatory system during SARS-CoV-2 infection, indicating possible antiviral therapeutics against SARS-CoV-2 through intervening miRNA regulation.

摘要

由严重急性呼吸综合征冠状病毒2（SARS-CoV-2）引起的2019冠状病毒病（COVID-19）正在全球范围内传播，其发病机制大多尚不清楚。病毒和宿主来源的微小RNA（miRNA）在病毒感染的病理过程中都起着重要作用。本研究旨在从miRNA的角度揭示SARS-CoV-2致病性的机制。我们在SARS-CoV-2基因组中搜索了潜在的miRNA基因和miRNA靶标，并进行实验以验证病毒编码的miRNA及其对潜在靶标的调控作用。其中一种病毒编码的miRNA，MR147-3p，过表达后导致病毒感染细胞中人类、、、和中所有预测靶标的转录水平显著降低。分析表明，免疫反应和细胞骨架组织是受感染调节的miRNA调控的两个最显著的生物学过程。此外，SARS-CoV-2的基因组突变导致了miRNA库和靶标的变化，表明miRNA在SARS-CoV-2进化过程中的减毒表型中可能发挥作用。本研究全面展示了SARS-CoV-2感染期间涉及miRNA的调控系统，提示通过干预miRNA调控可能产生针对SARS-CoV-2的抗病毒疗法。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/35ad/8193712/aee8edc53c53/jbr-35-3-216-6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/35ad/8193712/98d6c0c8b000/jbr-35-3-216-1.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/35ad/8193712/aee8edc53c53/jbr-35-3-216-6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/35ad/8193712/98d6c0c8b000/jbr-35-3-216-1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/35ad/8193712/c6408e1868d8/jbr-35-3-216-2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/35ad/8193712/ac8d1d2832f9/jbr-35-3-216-3.jpg
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