Molecular Virology Laboratory, Department of Medical Microbiology, Leiden University Medical Center, Leiden, The Netherlands.
Curr Top Microbiol Immunol. 2018;419:1-42. doi: 10.1007/82_2017_25.
Coronaviruses are pathogens with a serious impact on human and animal health. They mostly cause enteric or respiratory disease, which can be severe and life threatening, e.g., in the case of the zoonotic coronaviruses causing severe acute respiratory syndrome (SARS) and Middle East Respiratory Syndrome (MERS) in humans. Despite the economic and societal impact of such coronavirus infections, and the likelihood of future outbreaks of additional pathogenic coronaviruses, our options to prevent or treat coronavirus infections remain very limited. This highlights the importance of advancing our knowledge on the replication of these viruses and their interactions with the host. Compared to other +RNA viruses, coronaviruses have an exceptionally large genome and employ a complex genome expression strategy. Next to a role in basic virus replication or virus assembly, many of the coronavirus proteins expressed in the infected cell contribute to the coronavirus-host interplay. For example, by interacting with the host cell to create an optimal environment for coronavirus replication, by altering host gene expression or by counteracting the host's antiviral defenses. These coronavirus-host interactions are key to viral pathogenesis and will ultimately determine the outcome of infection. Due to the complexity of the coronavirus proteome and replication cycle, our knowledge of host factors involved in coronavirus replication is still in an early stage compared to what is known for some other +RNA viruses. This review summarizes our current understanding of coronavirus-host interactions at the level of the infected cell, with special attention for the assembly and function of the viral RNA-synthesising machinery and the evasion of cellular innate immune responses.
冠状病毒是对人类和动物健康具有严重影响的病原体。它们主要引起肠道或呼吸道疾病，这些疾病可能很严重且危及生命，例如，导致严重急性呼吸综合征（SARS）和中东呼吸综合征（MERS）的人畜共患冠状病毒。尽管此类冠状病毒感染会对经济和社会造成影响，并且很可能会有其他致病性冠状病毒的未来爆发，但我们预防或治疗冠状病毒感染的选择仍然非常有限。这突显了提高我们对这些病毒复制及其与宿主相互作用的认识的重要性。与其他+RNA 病毒相比，冠状病毒具有异常大的基因组，并采用复杂的基因组表达策略。除了在基本病毒复制或病毒组装中发挥作用外，感染细胞中表达的许多冠状病毒蛋白有助于冠状病毒-宿主相互作用。例如，通过与宿主细胞相互作用为冠状病毒复制创造最佳环境，通过改变宿主基因表达或抵抗宿主的抗病毒防御。这些冠状病毒-宿主相互作用是病毒发病机制的关键，最终将决定感染的结果。由于冠状病毒蛋白组和复制周期的复杂性，与其他一些+RNA 病毒相比，我们对参与冠状病毒复制的宿主因子的了解仍处于早期阶段。这篇综述总结了我们目前对感染细胞水平的冠状病毒-宿主相互作用的认识，特别关注病毒 RNA 合成机制的组装和功能以及细胞先天免疫反应的逃逸。
