Department of Ophthalmology and Visual Sciences, University of Illinois at Chicago, Chicago, IL, USA.
Department of Ophthalmology and Visual Sciences, University of Illinois at Chicago, Chicago, IL, USA; Department of Microbiology and Immunology, University of Illinois at Chicago, Chicago, IL 60612, USA.
Trends Microbiol. 2021 Mar;29(3):224-237. doi: 10.1016/j.tim.2020.12.007. Epub 2020 Dec 19.
Pathogens usurp host pathways to generate a permissive environment for their propagation. The current spread of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection presents the urgent need to understand the complex pathogen-host interplay for effective control of the virus. SARS-CoV-2 reorganizes the host cytoskeleton for efficient cell entry and controls host transcriptional processes to support viral protein translation. The virus also dysregulates innate cellular defenses using various structural and nonstructural proteins. This results in substantial but delayed hyperinflammation alongside a weakened interferon (IFN) response. We provide an overview of SARS-CoV-2 and its uniquely aggressive life cycle and discuss the interactions of various viral proteins with host signaling pathways. We also address the functional changes in SARS-CoV-2 proteins, relative to SARS-CoV. Our comprehensive assessment of host signaling in SARS-CoV-2 pathogenesis provides some complex yet important strategic clues for the development of novel therapeutics against this rapidly emerging worldwide crisis.
病原体篡夺宿主途径，为其繁殖生成一个许可的环境。目前严重急性呼吸综合征冠状病毒 2（SARS-CoV-2）感染的广泛传播迫切需要了解复杂的病原体-宿主相互作用，以有效控制病毒。SARS-CoV-2 重组宿主细胞骨架以实现有效的细胞进入，并控制宿主转录过程以支持病毒蛋白翻译。该病毒还利用各种结构和非结构蛋白来失调先天细胞防御。这导致大量但延迟的过度炎症以及干扰素（IFN）反应减弱。我们提供了 SARS-CoV-2 的概述及其独特的侵袭性生命周期，并讨论了各种病毒蛋白与宿主信号通路的相互作用。我们还讨论了 SARS-CoV-2 蛋白相对于 SARS-CoV 的功能变化。我们对 SARS-CoV-2 发病机制中宿主信号的全面评估为针对这一迅速出现的全球危机开发新型治疗方法提供了一些复杂但重要的战略线索。
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