Rando Halie M, MacLean Adam L, Lee Alexandra J, Lordan Ronan, Ray Sandipan, Bansal Vikas, Skelly Ashwin N, Sell Elizabeth, Dziak John J, Shinholster Lamonica, D'Agostino McGowan Lucy, Ben Guebila Marouen, Wellhausen Nils, Knyazev Sergey, Boca Simina M, Capone Stephen, Qi Yanjun, Park YoSon, Mai David, Sun Yuchen, Boerckel Joel D, Brueffer Christian, Byrd James Brian, Kamil Jeremy P, Wang Jinhui, Velazquez Ryan, Szeto Gregory L, Barton John P, Goel Rishi Raj, Mangul Serghei, Lubiana Tiago, Gitter Anthony, Greene Casey S
Department of Systems Pharmacology and Translational Therapeutics, University of Pennsylvania, Philadelphia, Pennsylvania, USA.
Department of Biochemistry and Molecular Genetics, University of Colorado School of Medicine, Aurora, Colorado, USA.
mSystems. 2021 Oct 26;6(5):e0009521. doi: 10.1128/mSystems.00095-21.
The novel coronavirus SARS-CoV-2, which emerged in late 2019, has since spread around the world and infected hundreds of millions of people with coronavirus disease 2019 (COVID-19). While this viral species was unknown prior to January 2020, its similarity to other coronaviruses that infect humans has allowed for rapid insight into the mechanisms that it uses to infect human hosts, as well as the ways in which the human immune system can respond. Here, we contextualize SARS-CoV-2 among other coronaviruses and identify what is known and what can be inferred about its behavior once inside a human host. Because the genomic content of coronaviruses, which specifies the virus's structure, is highly conserved, early genomic analysis provided a significant head start in predicting viral pathogenesis and in understanding potential differences among variants. The pathogenesis of the virus offers insights into symptomatology, transmission, and individual susceptibility. Additionally, prior research into interactions between the human immune system and coronaviruses has identified how these viruses can evade the immune system's protective mechanisms. We also explore systems-level research into the regulatory and proteomic effects of SARS-CoV-2 infection and the immune response. Understanding the structure and behavior of the virus serves to contextualize the many facets of the COVID-19 pandemic and can influence efforts to control the virus and treat the disease. COVID-19 involves a number of organ systems and can present with a wide range of symptoms. From how the virus infects cells to how it spreads between people, the available research suggests that these patterns are very similar to those seen in the closely related viruses SARS-CoV-1 and possibly Middle East respiratory syndrome-related CoV (MERS-CoV). Understanding the pathogenesis of the SARS-CoV-2 virus also contextualizes how the different biological systems affected by COVID-19 connect. Exploring the structure, phylogeny, and pathogenesis of the virus therefore helps to guide interpretation of the broader impacts of the virus on the human body and on human populations. For this reason, an in-depth exploration of viral mechanisms is critical to a robust understanding of SARS-CoV-2 and, potentially, future emergent human CoVs (HCoVs).
新型冠状病毒SARS-CoV-2于2019年末出现，此后在全球范围内传播，导致数亿人感染2019冠状病毒病（COVID-19）。虽然在2020年1月之前这种病毒种类尚不为人知，但它与其他感染人类的冠状病毒的相似性使得人们能够迅速深入了解其感染人类宿主的机制，以及人类免疫系统的反应方式。在此，我们将SARS-CoV-2置于其他冠状病毒的背景中，并确定关于其进入人类宿主后的行为已知的信息以及可以推断的信息。由于决定病毒结构的冠状病毒基因组内容高度保守，早期的基因组分析在预测病毒发病机制以及理解变异体之间的潜在差异方面提供了显著的先机。病毒的发病机制有助于深入了解症状学、传播和个体易感性。此外，先前对人类免疫系统与冠状病毒之间相互作用的研究已经确定了这些病毒如何逃避免疫系统的保护机制。我们还探讨了针对SARS-CoV-2感染和免疫反应的调控和蛋白质组学效应的系统层面研究。了解病毒的结构和行为有助于将COVID-19大流行的诸多方面置于背景中，并能够影响控制病毒和治疗疾病的努力。COVID-19涉及多个器官系统，可表现出广泛的症状。从病毒如何感染细胞到如何在人与人之间传播，现有研究表明这些模式与在密切相关的病毒SARS-CoV-1以及可能与中东呼吸综合征相关的冠状病毒（MERS-CoV）中观察到的模式非常相似。了解SARS-CoV-2病毒的发病机制也有助于将受COVID-19影响的不同生物系统之间的联系置于背景中。因此，探索病毒的结构、系统发育和发病机制有助于指导对病毒对人体和人群的更广泛影响的解读。出于这个原因,深入探索病毒机制对于全面了解SARS-CoV-2以及潜在的未来新出现的人类冠状病毒（HCoV）至关重要。
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