Rashid Mahamud-Ur, Glover Kathleen K M, Lao Ying, Spicer Victor, Coombs Kevin M
Department of Medical Microbiology and Infectious Diseases, University of Manitoba, Winnipeg, MB, Canada.
Manitoba Center for Proteomics and Systems Biology, Winnipeg, MB, Canada.
Front Microbiol. 2022 Oct 10;13:994512. doi: 10.3389/fmicb.2022.994512. eCollection 2022.
Newly re-emerging viruses are of significant global concern. In late 2019, a new coronavirus, SARS-CoV-2, emerged in China and soon spread worldwide, causing the COVID-19 pandemic, which to date has caused >6 M deaths. There has been a wealth of studies on this new virus since its emergence. The coronaviruses consist of many animal and human pathogens, with some of the human coronavirus, such as strain OC43, normally causing only mild cold-like symptoms. Viruses usurp host cellular processes to successfully replicate. We used tandem mass tag mass spectrometry-based proteomic analyses of human lung MRC-5 cells infected with OC43 for various periods of time to delineate virus-induced host cell alterations. Numerous proteins involved in lipid metabolism, molecular transport, small molecule biochemistry, cell death and survival, humoral immune response, and inflammatory response were dysregulated. Comparison of our findings to previous studies that examined a range of differentially pathogenic influenza A viruses (IAV), and to SARS-CoV-2 data, revealed that proteins involved in the cell cycle, cytokine signaling, DNA replication, and anti-inflammatory responses were generally similarly affected by virtually all tested IAV and CoV. However, proteins involved in necrosis, protein metabolism, ECM regulation, and signal transduction were generally different. In addition, the more pathogenic CoV and IAV activated Rb-dependent repression of E2F-mediated transcription, whereas less pathogenic influenza and coronaviruses either inhibited or had no effect on this pathway.
新出现的病毒引起了全球的重大关注。2019年末，一种新型冠状病毒SARS-CoV-2在中国出现，并迅速在全球传播，引发了COVID-19大流行，迄今为止已导致超过600万人死亡。自该病毒出现以来，已有大量关于它的研究。冠状病毒包括许多动物和人类病原体，其中一些人类冠状病毒，如OC43毒株，通常仅引起类似普通感冒的轻微症状。病毒会篡夺宿主细胞的过程以成功复制。我们对感染OC43不同时间段的人肺MRC-5细胞进行了基于串联质谱标签质谱分析的蛋白质组学分析，以描绘病毒诱导的宿主细胞变化。许多参与脂质代谢、分子运输、小分子生物化学、细胞死亡与存活、体液免疫反应和炎症反应的蛋白质表达失调。将我们的研究结果与之前研究一系列致病性不同的甲型流感病毒（IAV）以及SARS-CoV-2数据进行比较，发现参与细胞周期、细胞因子信号传导、DNA复制和抗炎反应的蛋白质通常受到几乎所有测试的IAV和冠状病毒的类似影响。然而，参与坏死、蛋白质代谢、细胞外基质调节和信号转导的蛋白质通常有所不同。此外，致病性更强的冠状病毒和IAV激活了Rb依赖的对E2F介导转录的抑制，而致病性较弱的流感病毒和冠状病毒则抑制该途径或对其没有影响。
