Department of Biochemistry and Molecular Biology , University of Texas Medical Branch , Galveston , Texas 77555 , United States.
Department of Molecular Genetics and Microbiology , Duke University , Durham , North Carolina 27710 , United States.
Chem Rev. 2018 Apr 25;118(8):4448-4482. doi: 10.1021/acs.chemrev.7b00719. Epub 2018 Apr 13.
Flaviviruses, such as dengue, Japanese encephalitis, tick-borne encephalitis, West Nile, yellow fever, and Zika viruses, are critically important human pathogens that sicken a staggeringly high number of humans every year. Most of these pathogens are transmitted by mosquitos, and not surprisingly, as the earth warms and human populations grow and move, their geographic reach is increasing. Flaviviruses are simple RNA-protein machines that carry out protein synthesis, genome replication, and virion packaging in close association with cellular lipid membranes. In this review, we examine the molecular biology of flaviviruses touching on the structure and function of viral components and how these interact with host factors. The latter are functionally divided into pro-viral and antiviral factors, both of which, not surprisingly, include many RNA binding proteins. In the interface between the virus and the hosts we highlight the role of a noncoding RNA produced by flaviviruses to impair antiviral host immune responses. Throughout the review, we highlight areas of intense investigation, or a need for it, and potential targets and tools to consider in the important battle against pathogenic flaviviruses.
黄病毒,如登革热、日本脑炎、蜱传脑炎、西尼罗河热、黄热病和寨卡病毒,是极为重要的人类病原体,每年都会使大量人群患病。这些病原体大多数通过蚊子传播,而且毫不奇怪,随着地球变暖、人口增长和迁移,它们的地理传播范围正在扩大。黄病毒是简单的 RNA-蛋白机器,与细胞脂质膜密切相关,进行蛋白质合成、基因组复制和病毒包装。在这篇综述中,我们研究了黄病毒的分子生物学,涉及病毒成分的结构和功能,以及这些成分如何与宿主因素相互作用。后者从功能上分为促病毒和抗病毒因素,其中都包括许多 RNA 结合蛋白。在病毒和宿主的界面上,我们强调了由黄病毒产生的非编码 RNA 来削弱抗病毒宿主免疫反应的作用。在整个综述中,我们强调了一些需要深入研究的领域,以及在对抗致病黄病毒的重要战斗中需要考虑的潜在靶点和工具。