Laboratory of Ultrastructural Virology, Institute for Life and Medical Sciences, Kyoto University, 53 Shogoin Kawahara-cho, Sakyo-ku, Kyoto 606-8507, Japan.
Laboratory of Ultrastructural Virology, Graduate School of Biostudies, Kyoto University, 53 Shogoin Kawahara-cho, Sakyo-ku, Kyoto 606-8507, Japan.
Microscopy (Oxf). 2023 Jun 8;72(3):178-190. doi: 10.1093/jmicro/dfac049.
Filoviruses are filamentous enveloped viruses belonging to the family Filoviridae, in the order Mononegavirales. Some filovirus members, such as Ebola virus and Marburg virus, cause severe hemorrhagic fever in humans and non-human primates. The filovirus ribonucleoprotein complex, called the nucleocapsid, forms a double-layered helical structure in which a non-segmented, single-stranded, negative-sense RNA genome is encapsidated by the nucleoprotein (NP), viral protein 35 (VP35), VP24, VP30 and RNA-dependent RNA polymerase (L). The inner layer consists of the helical NP-RNA complex, acting as a scaffold for the binding of VP35 and VP24 that constitute the outer layer. Recent structural studies using cryo-electron microscopy have advanced our understanding of the molecular mechanism of filovirus nucleocapsid formation. Here, we review the key characteristics of the Ebola virus and Marburg virus nucleocapsid structures, highlighting the similarities and differences between the two viruses. In particular, we focus on the structure of the helical NP-RNA complex, the RNA binding mechanism and the NP-NP interactions in the helix. The structural analyses reveal a possible mechanism of nucleocapsid assembly and provide potential targets for the anti-filovirus drug design.
丝状病毒是丝状包膜病毒，属于丝状病毒科，单负链病毒目。一些丝状病毒成员，如埃博拉病毒和马尔堡病毒，会导致人类和非人类灵长类动物出现严重的出血热。丝状病毒的核糖核蛋白复合物，称为核衣壳，形成双层螺旋结构，其中非分段、单链、负义 RNA 基因组被核蛋白（NP）、病毒蛋白 35（VP35）、VP24、VP30 和 RNA 依赖的 RNA 聚合酶（L）包裹。内层由螺旋 NP-RNA 复合物组成，作为结合 VP35 和 VP24 的支架，VP35 和 VP24 构成外层。最近使用冷冻电子显微镜的结构研究提高了我们对丝状病毒核衣壳形成的分子机制的理解。在这里，我们回顾了埃博拉病毒和马尔堡病毒核衣壳结构的关键特征，强调了这两种病毒之间的相似之处和不同之处。特别是，我们专注于螺旋 NP-RNA 复合物的结构、RNA 结合机制以及螺旋中的 NP-NP 相互作用。结构分析揭示了核衣壳组装的可能机制，并为抗丝状病毒药物设计提供了潜在的靶点。
