State Key Laboratory of Medical Molecular Biology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences and School of Basic Medicine, Peking Union Medical College, Beijing, 100005, China.
Department of Biochemistry and Molecular Biology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences and School of Basic Medicine, Peking Union Medical College, Beijing, 100005, China.
Cell Mol Life Sci. 2021 Jun;78(11):4939-4954. doi: 10.1007/s00018-021-03834-6. Epub 2021 Apr 12.
Flaviviruses are positive-sense single-stranded RNA viruses that pose a considerable threat to human health. Flaviviruses replicate in compartmentalized replication organelles derived from the host endoplasmic reticulum (ER). The characteristic architecture of flavivirus replication organelles includes invaginated vesicle packets and convoluted membrane structures. Multiple factors, including both viral proteins and host factors, contribute to the biogenesis of the flavivirus replication organelle. Several viral nonstructural (NS) proteins with membrane activity induce ER rearrangement to build replication compartments, and other NS proteins constitute the replication complexes (RC) in the compartments. Host protein and lipid factors facilitate the formation of replication organelles. The lipid membrane, proteins and viral RNA together form the functional compartmentalized replication organelle, in which the flaviviruses efficiently synthesize viral RNA. Here, we reviewed recent advances in understanding the structure and biogenesis of flavivirus replication organelles, and we further discuss the function of virus NS proteins and related host factors as well as their roles in building the replication organelle.
黄病毒是正链单链 RNA 病毒，对人类健康构成重大威胁。黄病毒在源自宿主内质网 (ER) 的分隔复制细胞器中复制。黄病毒复制细胞器的特征结构包括内陷的囊泡包和卷曲的膜结构。多种因素，包括病毒蛋白和宿主因子，有助于黄病毒复制细胞器的生物发生。几种具有膜活性的病毒非结构 (NS) 蛋白诱导 ER 重排以构建复制隔间，而其他 NS 蛋白在隔间中构成复制复合物 (RC)。宿主蛋白和脂质因子促进复制细胞器的形成。脂质膜、蛋白质和病毒 RNA 共同形成功能性分隔复制细胞器，黄病毒在其中有效地合成病毒 RNA。在这里，我们综述了对黄病毒复制细胞器的结构和生物发生的理解的最新进展，我们还进一步讨论了病毒 NS 蛋白和相关宿主因子的功能及其在构建复制细胞器中的作用。
