Dansako Hiromichi, Hiramoto Hiroki, Ikeda Masanori, Wakita Takaji, Kato Nobuyuki
Department of Tumor Virology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, 2-5-1 Shikata-cho, Kita-ku, Okayama 700-8558, Japan.
Department of Virology II, National Institute of Infectious Disease, 1-23-1 Toyama, Shinjuku-ku, Tokyo 162-8640, Japan.
Virology. 2014 Aug;462-463:166-74. doi: 10.1016/j.virol.2014.05.017. Epub 2014 Jul 3.
During persistent infection of HCV, the HCV core protein (HCV-JFH-1 strain of genotype 2a) is recruited to lipid droplets (LDs) for viral assembly, but the mechanism of recruitment of the HCV core protein is uncertain. Here, we demonstrated that one of the Ras-related small GTPases, Rab18, was required for trafficking of the core protein around LDs. The knockdown of Rab18 reduced intracellular and extracellular viral infectivity, but not intracellular viral replication in HCV-JFH-1-infected RSc cells (an HuH-7-derived cell line). Exogenous expression of Rab18 increased extracellular viral infectivity almost two-fold. Furthermore, Rab18 was co-localized with the core protein in HCV-JFH-1-infected RSc cells, and the knockdown of Rab18 blocked recruitment of the HCV-JFH-1 core protein to LDs. These results suggest that Rab18 has an important role in viral assembly through the trafficking of the core protein to LDs.
在丙型肝炎病毒（HCV）持续感染期间，HCV核心蛋白（2a基因型的HCV-JFH-1毒株）被募集到脂滴（LDs）用于病毒组装，但HCV核心蛋白的募集机制尚不确定。在此，我们证明了一种Ras相关的小GTP酶Rab18是核心蛋白在脂滴周围运输所必需的。敲低Rab18可降低HCV-JFH-1感染的RSc细胞（一种源自HuH-7的细胞系）的细胞内和细胞外病毒感染性，但不影响细胞内病毒复制。Rab18的外源性表达使细胞外病毒感染性增加了近两倍。此外，在HCV-JFH-1感染的RSc细胞中，Rab18与核心蛋白共定位，敲低Rab18可阻止HCV-JFH-1核心蛋白募集到脂滴。这些结果表明，Rab18通过将核心蛋白运输到脂滴在病毒组装中起重要作用。
