Rab18 is required for viral assembly of hepatitis C virus through trafficking of the core protein to lipid droplets

被引:48
作者
Dansako, Hiromichi [1 ]
Hiramoto, Hiroki [1 ]
Ikeda, Masanori [1 ]
Wakita, Takaji [2 ]
Kato, Nobuyuki [1 ]
机构
[1] Okayama Univ, Grad Sch Med Dent & Pharmaceut Sci, Dept Tumor Virol, Kita Ku, Okayama 7008558, Japan
[2] Natl Inst Infect Dis, Dept Virol 2, Shinjuku Ku, Tokyo 1628640, Japan
基金
日本学术振兴会;
关键词
Hepatitis C virus; Rab18; Viral assembly; Lipid droplet; Core protein; RNA replication; RNA REPLICATION; HUMAN HEPATOCYTES; CELL-CULTURE; NON-A; INTERFERON; MEMBRANE; GENOME; SYSTEM; ACTIVATION; TIP47;
D O I
10.1016/j.virol.2014.05.017
中图分类号
Q93 [微生物学];
学科分类号
071005 ; 100705 ;
摘要
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. (C) 2014 Elsevier Inc. All rights reserved.
引用
收藏
页码:166 / 174
页数:9
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