Key Laboratory of Special Pathogens and Biosafety, Wuhan Institute of Virology, Center for Biosafety Mega-Science, Chinese Academy of Sciences, No. 262 Jin Long Street, Wuhan, Hubei 430207, China.
University of Chinese Academy of Sciences, Beijing 100049, China.
Nucleic Acids Res. 2024 Apr 12;52(6):3278-3290. doi: 10.1093/nar/gkae042.
Jingmenviruses are a category of emerging segmented viruses that have garnered global attention in recent years, and are close relatives of the flaviviruses in the Flaviviridae family. One of their genome segments encodes NSP1 homologous to flavivirus NS5. NSP1 comprises both the methyltransferase (MTase) and RNA-dependent RNA polymerase (RdRP) modules playing essential roles in viral genome replication and capping. Here we solved a 1.8-Å resolution crystal structure of the NSP1 RdRP module from Jingmen tick virus (JMTV), the type species of jingmenviruses. The structure highly resembles flavivirus NS5 RdRP despite a sequence identity less than 30%. NSP1 RdRP enzymatic properties were dissected in a comparative setting with several representative Flaviviridae RdRPs included. Our data indicate that JMTV NSP1 produces characteristic 3-mer abortive products similar to the hepatitis C virus RdRP, and exhibits the highest preference of terminal initiation and shorter-primer usage. Unlike flavivirus NS5, JMTV RdRP may require the MTase for optimal transition from initiation to elongation, as an MTase-less NSP1 construct produced more 4-5-mer intermediate products than the full-length protein. Taken together, this work consolidates the evolutionary relationship between the jingmenvirus group and the Flaviviridae family, providing a basis to the further understanding of their viral replication/transcription process.
荆门人病毒是一类新兴的分段病毒，近年来引起了全球关注，它们是黄病毒科黄病毒的近亲。其基因组的一个片段编码与黄病毒 NS5 同源的非结构蛋白 1（NSP1）。NSP1 包含甲基转移酶（MTase）和 RNA 依赖性 RNA 聚合酶（RdRP）两个模块，在病毒基因组复制和加帽过程中发挥重要作用。在此，我们解析了荆门人病毒（JMTV）NSP1 RdRP 模块的 1.8Å 分辨率晶体结构，JMTV 是荆门人病毒属的代表种。尽管序列同一性小于 30%，但该结构与黄病毒 NS5 RdRP 高度相似。我们在包含几种代表性黄病毒科 RdRP 的比较环境中对 NSP1 RdRP 的酶学特性进行了剖析。数据表明，JMTV NSP1 产生特征性的 3 聚体终止产物，类似于丙型肝炎病毒 RdRP，并表现出最高的末端起始偏好和较短的引物使用偏好。与黄病毒 NS5 不同，JMTV RdRP 可能需要 MTase 才能从起始到延伸进行最佳转变，因为无 MTase 的 NSP1 构建体产生的 4-5 聚体中间产物比全长蛋白多。总之，这项工作巩固了荆门人病毒属与黄病毒科之间的进化关系，为进一步了解它们的病毒复制/转录过程提供了基础。
