Key Laboratory of Zoonosis Research, Ministry of Education, Institute of Zoonosis, College of Veterinary Medicine, Jilin University, 5333 Xian Road, Changchun 130062, China.
Virus Res. 2019 Apr 2;263:217-225. doi: 10.1016/j.virusres.2019.02.006. Epub 2019 Feb 14.
Rabies virus (RABV), an enveloped virus with a single-stranded and negative-sense RNA genome, is the type species of the Lyssavirus Genus within the Rhabdoviridae family. As the causative agent of rabies with a nearly 100% fatality, the neurotropic RABV pose a serious threat to the global public health. Though a great effort has been made toward understanding the molecular mechanism underlying virus infection cycle, there are still many aspects need to be elucidated, especially on the early events during virus replication cycle. With the application of the multiple advanced technologies, much progress has been made on these aspects. To date, multiple receptors, such as nAChR, NCAM, p75NTR, mGluR2, carbohydrates, and gangliosides, have been identified. Following initial attachment, RABV internalization occurs through clathrin-mediated endocytosis (CME) with the help of actin. After viral entry, intracellular trafficking occurs. Two retrograde trafficking models, stating that either whole virions are parceled into vesicles or only the viral capsids are transported, have been proposed. Moreover, complete enveloped virions or G-containing vesicle-associated ribonucleoproteins (RNPs) may be formed during anterograde transport, which remains poorly characterized but is important for viral budding. Combining the data elucidating the molecular mechanisms of RABV attachment, entry, and intracellular trafficking, this review provides an integrated view of the early events in the viral life cycle.
狂犬病病毒（Rabies virus，RABV）是一种具有单链和负义 RNA 基因组的包膜病毒，是 Rhabdoviridae 科中的 Lyssavirus 属的模式种。作为狂犬病的病原体，具有近 100%的致死率，神经嗜性的 RABV 对全球公共卫生构成严重威胁。尽管人们已经做出了巨大的努力来了解病毒感染周期的分子机制，但仍有许多方面需要阐明，尤其是在病毒复制周期的早期事件方面。随着多种先进技术的应用，在这些方面已经取得了很大的进展。迄今为止，已经鉴定出多种受体，如 nAChR、NCAM、p75NTR、mGluR2、碳水化合物和神经节苷脂。在初始附着之后，RABV 通过网格蛋白介导的内吞作用（clathrin-mediated endocytosis，CME）在肌动蛋白的帮助下发生内化。病毒进入后，会发生细胞内运输。提出了两种逆行运输模型，一种是整个病毒颗粒被包裹成囊泡，另一种是只有病毒衣壳被运输。此外，在顺行运输过程中可能会形成完整的包膜病毒或含有 G 的囊泡相关核糖核蛋白（ribonucleoprotein，RNP），但这一过程尚未得到很好的描述，但对于病毒出芽很重要。结合阐明 RABV 附着、进入和细胞内运输分子机制的数据，本文综述了病毒生命周期早期事件的综合观点。
