Data_Sheet_1_Temporal proteomic analyses of human lung cells distinguish high pathogenicity influenza viruses and coronaviruses from low pathogenicity viruses.xlsx

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.

新型再现病毒已成为全球范围内的重大关切问题。2019年末，新型冠状病毒（SARS-CoV-2）于中国首次出现并迅速在全球蔓延，引发新冠肺炎（COVID-19）大流行，迄今已造成超600万人死亡。自该病毒出现以来，学界已针对其开展了大量研究。冠状病毒科包含多种动物及人类病原体，其中部分人类冠状病毒（如OC43毒株）通常仅引发类似普通感冒的轻微症状。病毒通过篡夺宿主细胞的生命活动过程以实现高效复制。本研究采用基于串联质量标签（tandem mass tag, TMT）质谱的蛋白质组学分析方法，对感染OC43毒株不同时长的人类肺MRC-5细胞进行检测，以阐明病毒诱导的宿主细胞变化。大量参与脂质代谢、分子转运、小分子生物化学过程、细胞死亡与存活、体液免疫应答及炎症应答的蛋白质均出现表达失调。将本研究结果与此前针对不同致病力甲型流感病毒（influenza A virus, IAV）的相关研究，以及SARS-CoV-2相关数据进行对比后发现，几乎所有受试的IAV和冠状病毒均可对参与细胞周期、细胞因子信号通路、DNA复制及抗炎应答的蛋白质产生相似影响。但涉及细胞坏死、蛋白质代谢、细胞外基质（extracellular matrix, ECM）调控及信号转导的蛋白质则通常呈现不同的表达变化模式。此外，高致病力的冠状病毒与IAV均可激活依赖于Rb的E2F介导转录抑制通路，而低致病力的流感病毒与冠状病毒则对该通路产生抑制或无显著影响。