Department of Molecular Biology and Microbiology, Case Western Reserve University School of Medicine, Cleveland, OH 44106, USA.
Department of Inflammation and Immunity, Lerner Research Institute, Cleveland Clinic, Cleveland, OH 44195, USA.
Viruses. 2019 Jun 1;11(6):504. doi: 10.3390/v11060504.
Rabies virus (RABV) is a causative agent of a fatal neurological disease in humans and animals. The large (L) protein of RABV is a multifunctional RNA-dependent RNA polymerase, which is one of the most attractive targets for developing antiviral agents. A remarkable homology of the RABV L protein to a counterpart in vesicular stomatitis virus, a well-characterized rhabdovirus, suggests that it catalyzes mRNA processing reactions, such as 5'-capping, cap methylation, and 3'-polyadenylation, in addition to RNA synthesis. Recent breakthroughs in developing in vitro RNA synthesis and capping systems with a recombinant form of the RABV L protein have led to significant progress in our understanding of the molecular mechanisms of RABV RNA biogenesis. This review summarizes functions of RABV replication proteins in transcription and replication, and highlights new insights into roles of an unconventional mRNA capping enzyme, namely GDP polyribonucleotidyltransferase, domain of the RABV L protein in mRNA capping and transcription initiation.
狂犬病病毒（RABV）是一种导致人类和动物致命神经疾病的病原体。RABV 的大（L）蛋白是一种多功能的 RNA 依赖性 RNA 聚合酶，是开发抗病毒药物最具吸引力的靶标之一。RABV L 蛋白与水疱性口炎病毒（一种特征明确的弹状病毒）的对应物具有显著的同源性，表明它除了 RNA 合成之外，还催化 mRNA 加工反应，如 5'-加帽、帽甲基化和 3'-多聚腺苷酸化。最近在使用重组 RABV L 蛋白开发体外 RNA 合成和加帽系统方面取得的突破，使我们对 RABV RNA 生物发生的分子机制有了更深入的了解。本文综述了 RABV 复制蛋白在转录和复制中的功能，并强调了 RABV L 蛋白中非传统的 mRNA 加帽酶（即 GDP 多核糖核苷酸转移酶）在 mRNA 加帽和转录起始中的作用的新见解。
