受感染猕猴多个器官中 SARS-CoV-2 变异体的转录组差异景观

IF 11.5 2区 生物学 Q1 GENETICS & HEREDITY Genomics, Proteomics & Bioinformatics Pub Date : 2023-10-01 Epub Date: 2023-07-13 DOI:10.1016/j.gpb.2023.06.002
Tingfu Du, Chunchun Gao, Shuaiyao Lu, Qianlan Liu, Yun Yang, Wenhai Yu, Wenjie Li, Yong Qiao Sun, Cong Tang, Junbin Wang, Jiahong Gao, Yong Zhang, Fangyu Luo, Ying Yang, Yun-Gui Yang, Xiaozhong Peng
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引用次数: 0

摘要

严重急性呼吸系统综合征冠状病毒 2(SARS-CoV-2)导致了 2019 年冠状病毒病(COVID-19)的持续大流行,造成全球数百万人死亡,并带来了巨大的公共卫生和全球经济负担。SARS-CoV-2的变种不断增多,加剧了全球反复出现的感染浪潮。本研究阐明了 SARS-CoV-2 原始株及其相关变异株(VOCs,包括 Alpha、Beta 和 Delta)在体外的病毒学特征,以及受感染猕猴多个器官(肺、右心室、血液、大脑皮层和小脑)的不同转录组景观。SARS-CoV-2 原始毒株会引起宿主细胞更强的先天性免疫反应,其 VOCs 会显著增加亚基因组 RNA 的水平,如 N、Orf9b、Orf6 和 Orf7ab,这些 RNA 被称为先天性免疫拮抗剂和抗病毒因子抑制剂。有趣的是,SARS-CoV-2 原始菌株和 Alpha 菌株在恒河猴组织中诱导的 RNA 丰度变化比 Beta 和 Delta 变体更大。此外,右心室中炎症和免疫相关 RNA 的上调显示了高炎症状态和活跃的免疫反应。此外,外周血可能介导组织间的信号传递,以协调受感染个体的分子变化。总之,这些数据为了解 SARS-CoV-2 原始菌株及其 VOCs 在感染早期的发病机理提供了重要信息。
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Differential Transcriptomic Landscapes of SARS-CoV-2 Variants in Multiple Organs from Infected Rhesus Macaques.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) caused the persistent coronavirus disease 2019 (COVID-19) pandemic, which has resulted in millions of deaths worldwide and brought an enormous public health and global economic burden. The recurring global wave of infections has been exacerbated by growing variants of SARS-CoV-2. In this study, the virological characteristics of the original SARS-CoV-2 strain and its variants of concern (VOCs; including Alpha, Beta, and Delta) in vitro, as well as differential transcriptomic landscapes in multiple organs (lung, right ventricle, blood, cerebral cortex, and cerebellum) from the infected rhesus macaques, were elucidated. The original strain of SARS-CoV-2 caused a stronger innate immune response in host cells, and its VOCs markedly increased the levels of subgenomic RNAs, such as N, Orf9b, Orf6, and Orf7ab, which are known as the innate immune antagonists and the inhibitors of antiviral factors. Intriguingly, the original SARS-CoV-2 strain and Alpha variant induced larger alteration of RNA abundance in tissues of rhesus monkeys than Beta and Delta variants did. Moreover, a hyperinflammatory state and active immune response were shown in the right ventricles of rhesus monkeys by the up-regulation of inflammation- and immune-related RNAs. Furthermore, peripheral blood may mediate signaling transmission among tissues to coordinate the molecular changes in the infected individuals. Collectively, these data provide insights into the pathogenesis of COVID-19 at the early stage of infection by the original SARS-CoV-2 strain and its VOCs.

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来源期刊
Genomics, Proteomics & Bioinformatics
Genomics, Proteomics & Bioinformatics Biochemistry, Genetics and Molecular Biology-Biochemistry
CiteScore
14.30
自引率
4.20%
发文量
844
审稿时长
61 days
期刊介绍: Genomics, Proteomics and Bioinformatics (GPB) is the official journal of the Beijing Institute of Genomics, Chinese Academy of Sciences / China National Center for Bioinformation and Genetics Society of China. It aims to disseminate new developments in the field of omics and bioinformatics, publish high-quality discoveries quickly, and promote open access and online publication. GPB welcomes submissions in all areas of life science, biology, and biomedicine, with a focus on large data acquisition, analysis, and curation. Manuscripts covering omics and related bioinformatics topics are particularly encouraged. GPB is indexed/abstracted by PubMed/MEDLINE, PubMed Central, Scopus, BIOSIS Previews, Chemical Abstracts, CSCD, among others.
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