Transcriptomic profiling and genomic mutational analysis of Human coronavirus (HCoV)-229E -infected human cells.
Transcriptomic profiling and genomic mutational analysis of Human coronavirus (HCoV)-229E -infected human cells.
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DOI：
10.1371/journal.pone.0247128
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发表时间：
2021
期刊：
影响因子：
3.7
通讯作者：
Mandelboim M
中科院分区：
文献类型：
--
作者：
Friedman N;Jacob-Hirsch J;Drori Y;Eran E;Kol N;Nayshool O;Mendelson E;Rechavi G;Mandelboim M
人类冠状病毒(HCoV)会引起轻微到严重的呼吸道感染。大多数常见感冒疾病是由四种HCoV中的一种引起的，即HCoV-229E、HCoV-NL63、HCoV-HKU1和HCoV-OC43。一些研究已经应用全球转录转录方法来了解宿主对HCoV感染的反应，大多数研究集中在大流行严重急性呼吸综合征冠状病毒(SARS-CoV)、中东呼吸综合征冠状病毒(MERS-CoV)和新出现的SARS-CoV-2上。在这项研究中，下一代测序被用来获得对甲型冠状病毒HCoV-229E引起的细胞转录变化的新见解。HCoV-229E感染的MRC-5细胞胆固醇生物合成超通路和eIF2信号通路明显下调。此外，Cyclins的上调、细胞周期对染色体复制的控制以及BRCA1在DNA损伤反应中的作用，以及细胞周期G1/S检查点的下调，提示HCoV229E可能有利于病毒感染的S期。有趣的是，在HCoV-229E感染的早期，细胞天然免疫的关键因子、干扰素刺激基因(ISGs)和其他早期抗病毒反应基因的转录产物都下调了。另一方面，抗病毒反应因子ApoB mRNA编辑酶催化亚基3B(APOBEC3B)早期表达上调。以前在SARS-CoV-2基因组分析中发现了APOBEC3B胞苷脱氨酶信号(C-to-T)，但没有观察到HCoV-229E。在SARS-CoV-2造成高死亡率的国家中，发现了更高水平的C-T突变。APOBEC的活动可能成为新出现的CoV的标志。这项研究将加强我们对常见传播的HCoV的了解，并有望提供关于仍在出现的冠状病毒的关键信息。
Human coronaviruses (HCoVs) cause mild to severe respiratory infection. Most of the common cold illnesses are caused by one of four HCoVs, namely HCoV-229E, HCoV-NL63, HCoV-HKU1 and HCoV-OC43. Several studies have applied global transcriptomic methods to understand host responses to HCoV infection, with most studies focusing on the pandemic severe acute respiratory syndrome coronavirus (SARS-CoV), Middle East respiratory syndrome CoV (MERS-CoV) and the newly emerging SARS-CoV-2. In this study, Next Generation Sequencing was used to gain new insights into cellular transcriptomic changes elicited by alphacoronavirus HCoV-229E. HCoV-229E-infected MRC-5 cells showed marked downregulation of superpathway of cholesterol biosynthesis and eIF2 signaling pathways. Moreover, upregulation of cyclins, cell cycle control of chromosomal replication, and the role of BRCA1 in DNA damage response, alongside downregulation of the cell cycle G1/S checkpoint, suggest that HCoV-229E may favors S phase for viral infection. Intriguingly, a significant portion of key factors of cell innate immunity, interferon-stimulated genes (ISGs) and other transcripts of early antiviral response genes were downregulated early in HCoV-229E infection. On the other hand, early upregulation of the antiviral response factor Apolipoprotein B mRNA editing enzyme catalytic subunit 3B (APOBEC3B) was observed. APOBEC3B cytidine deaminase signature (C-to-T) was previously observed in genomic analysis of SARS-CoV-2 but not HCoV-229E. Higher levels of C-to-T mutations were found in countries with high mortality rates caused by SARS-CoV-2. APOBEC activity could be a marker for new emerging CoVs. This study will enhance our understanding of commonly circulating HCoVs and hopefully provide critical information about still-emerging coronaviruses.
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DOI：
10.1007/978-1-4939-0888-2_10
发表时间：
2014
期刊：
Methods in molecular biology (Clifton, N.J.)
影响因子：
--
作者：
Bagga S;Bouchard MJ
通讯作者：
Bouchard MJ
影响因子：
28.3
作者：
Gorbalenya, Alexander E.;Baker, Susan C.;Ziebuhr, John
通讯作者：
Ziebuhr, John
影响因子：
5.4
作者：
Chen, CJ;Makino, S
通讯作者：
Makino, S
影响因子：
9
作者：
Channappanavar R;Perlman S
通讯作者：
Perlman S
影响因子：
--
作者：
de Wilde AH;Snijder EJ;Kikkert M;van Hemert MJ
通讯作者：
van Hemert MJ