Epitranscriptomic m6A profile of SARS-CoV-2-infected human lung epithelial cells

SARS-CoV-2感染的人肺上皮细胞的表观转录组m6A谱

基本信息

批准号：
10297640
负责人：
Li Wu
金额：
$ 19.31万
依托单位：
UNIVERSITY OF IOWA
依托单位国家：
美国
项目类别：
财政年份：
2021
资助国家：
美国
起止时间：
2021-06-01 至 2023-05-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10297640
关键词：
2019-nCoV Address Affect Antiviral Agents Attenuated Bioinformatics COVID-19 COVID-19 pandemic COVID-19 pathogenesis COVID-19 treatment Cells Chemicals Clinical Collaborations Coronavirus Coronavirus Infections Cytokine Gene Data Development Epithelial Cells Foundations Future Gene Expression Gene Expression Regulation Genes HIV-1 Hour Human Immune Evasion Immunoprecipitation Infection Inflammatory Interferon Type I Interferons Italy Left Length Lung Maps Messenger RNA Modification Molecular Nucleotides Organism Pathogenicity Patients Pharmaceutical Preparations Play Post-Transcriptional Regulation RNA Regulation Role SARS-CoV-2 genome SARS-CoV-2 infection Site Technology Testing Vaccines Viral Genes Viral Genome Viral Pathogenesis Virus Virus Replication base cellular targeting cytokine cytokine release syndrome epitranscriptomics genomic RNA global health health economics mRNA Expression mutant new therapeutic target novel prevent severe COVID-19 therapeutically effective transcriptome sequencing vaccine candidate

项目摘要

Abstract The COVID-19 pandemic caused by severe acute respiratory syndrome-related coronavirus 2 (SARS-CoV-2) has resulted in global health and economic crises. To develop effective vaccines and antivirals to prevent and control SARS-CoV-2 or other coronavirus infections, it is critical to understand the regulatory mechanisms of SARS-CoV-2 genome replication in host cells. In this R21 project, we will use novel epitranscriptomic technologies to investigate SARS-CoV-2 replication in human lung epithelial cells. N6-methyladenosine (m6A) modifications of many viruses play a major role in epitranscriptomic regulation of viral replication, gene expression, and immune evasion. However, it is unclear whether and how m6A modifications of the SARS-CoV-2 genome and cellular genes affect viral replication and pathogenicity. Our preliminary studies showed that SARS-CoV-2 infection of human lung epithelial cells upregulated m6A levels in cellular RNA. Our bioinformatic analysis of 13,699 full-length SARS- CoV-2 genome sequences predicts multiple m6A modification sites that are highly conserved among SARS-CoV-2 isolates worldwide. Thus, we hypothesize that m6A modifications of the SARS-CoV-2 genome and cellular genes enhance viral replication in cells through epitranscriptomic regulation. We propose two specific aims to test this hypothesis. Aim 1. To investigate the m6A epitranscriptomic profile of SARS-CoV-2-infected lung epithelial cells; Aim 2. To map m6A sites on the SARS-CoV-2 genome and to identify critical sites for viral replication. Defining epitranscriptomic m6A profile of SARS-CoV-2-infected cells has significant implications in understanding the COVID-19 pathogenesis and identifying novel drug targets.

抽象的严重急性呼吸综合症相关的冠状病毒2 （SARS-COV-2）导致全球健康和经济危机。开发有效的疫苗和防止和控制SARS-COV-2或其他冠状病毒感染的抗病毒药了解宿主细胞中SARS-COV-2基因组复制的调节机制。在这个 R21项目，我们将使用新颖的表面参考技术研究SARS-COV-2 人肺上皮细胞中的复制。 N6-甲基腺苷（M6A）的修饰病毒在病毒复制，基因表达和表达的表面参考调节中起主要作用免疫逃避。但是，目前尚不清楚SARS-COV-2的M6A是否修改基因组和细胞基因会影响病毒复制和致病性。我们的初步研究表明，人肺上皮细胞的SARS-COV-2感染细胞RNA中的M6A水平上调。我们对13,699个全长SARS-的生物信息学分析 - COV-2基因组序列预测了高度保守的多个M6A修饰位点在全球SARS-COV-2分离物中。因此，我们假设M6A的修改 SARS-COV-2基因组和细胞基因通过同意调节。我们提出了两个特定的目的来检验这一假设。目标1 研究SARS-COV-2感染的肺上皮细胞的M6a同意分析谱；目标2。在SARS-COV-2基因组上绘制M6A位点，并识别病毒复制的关键位点。定义SARS-COV-2感染细胞的表面参考的M6A特征具有显着意义在理解COVID-19的发病机理和识别新型药物靶标时。