The lipid droplet is an important organelle for hepatitis C virus production

被引:977
作者
Miyanari, Yusuke
Atsuzawa, Kimie
Usuda, Nobuteru
Watashi, Koichi
Hishiki, Takayuki
Zayas, Margarita
Bartenschlager, Ralf
Wakita, Takaji
Hijikata, Makoto
Shimotohno, Kunitada [1 ]
机构
[1] Kyoto Univ, Inst Virus Res, Dept Viral Oncol, Kyoto 6068507, Japan
[2] Kyoto Univ, Grad Sch Biostudies, Kyoto 6068507, Japan
[3] Fujita Hlth Univ, Dept Anat, Toyoake, Aichi 4701192, Japan
[4] Heidelberg Univ, Dept Mol Biol, D-69120 Heidelberg, Germany
[5] Natl Inst Infect Dis, Dept Virol 2, Tokyo, Japan
基金
日本学术振兴会;
关键词
CORE PROTEIN; CELL-LINES; REPLICATION; IDENTIFICATION; EXPRESSION; SURFACE; GENOME;
D O I
10.1038/ncb1631
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
摘要
The lipid droplet (LD) is an organelle that is used for the storage of neutral lipids. It dynamically moves through the cytoplasm, interacting with other organelles, including the endoplasmic reticulum ( ER)(1-3). These interactions are thought to facilitate the transport of lipids and proteins to other organelles. The hepatitis C virus (HCV) is a causative agent of chronic liver diseases(4). HCV capsid protein ( Core) associates with the LD5, envelope proteins E1 and E2 reside in the ER lumen(6), and the viral replicase is assumed to localize on ER- derived membranes. How and where HCV particles are assembled, however, is poorly understood. Here, we show that the LD is involved in the production of infectious virus particles. We demonstrate that Core recruits nonstructural (NS) proteins and replication complexes to LD-associated membranes, and that this recruitment is critical for producing infectious viruses. Furthermore, virus particles were observed in close proximity to LDs, indicating that some steps of virus assembly take place around LDs. This study reveals a novel function of LDs in the assembly of infectious HCV and provides a new perspective on how viruses usurp cellular functions.
引用
收藏
页码:1089 / U74
页数:22
相关论文
共 28 条
  • [1] BLANCHETTEMACKIE EJ, 1995, J LIPID RES, V36, P1211
  • [2] Highly permissive cell lines for subgenomic and genomic hepatitis C virus RNA replication
    Blight, KJ
    McKeating, JA
    Rice, CM
    [J]. JOURNAL OF VIROLOGY, 2002, 76 (24) : 13001 - 13014
  • [3] Formation of native hepatitis C virus glycoprotein complexes
    Deleersnyder, V
    Pillez, A
    Wychowski, C
    Blight, K
    Xu, J
    Hahn, YS
    Rice, CM
    Dubuisson, J
    [J]. JOURNAL OF VIROLOGY, 1997, 71 (01) : 697 - 704
  • [4] Interaction of hepatitis C virus proteins with host cell membranes and lipids
    Dubuisson, J
    Penin, F
    Moradpour, D
    [J]. TRENDS IN CELL BIOLOGY, 2002, 12 (11) : 517 - 523
  • [5] Expression of hepatitis C virus proteins induces distinct membrane alterations including a candidate viral replication complex
    Egger, D
    Wölk, B
    Gosert, R
    Bianchi, L
    Blum, HE
    Moradpour, D
    Bienz, K
    [J]. JOURNAL OF VIROLOGY, 2002, 76 (12) : 5974 - 5984
  • [6] Hijikata M, 1993, Uirusu, V43, P293
  • [7] The domains required to direct core proteins of hepatitis C virus and GB virus-B to lipid droplets share common features with plant oleosin proteins
    Hope, RG
    Murphy, DJ
    McLauchlan, J
    [J]. JOURNAL OF BIOLOGICAL CHEMISTRY, 2002, 277 (06) : 4261 - 4270
  • [8] Diverse effects of cyclosporine on hepatitis C virus strain replication
    Ishii, N
    Watashi, K
    Hishiki, T
    Goto, K
    Inoue, D
    Hijikata, M
    Wakita, T
    Kato, N
    Shimotohno, K
    [J]. JOURNAL OF VIROLOGY, 2006, 80 (09) : 4510 - 4520
  • [9] MOLECULAR-CLONING OF THE HUMAN HEPATITIS-C VIRUS GENOME FROM JAPANESE PATIENTS WITH NON-A, NON-B HEPATITIS
    KATO, N
    HIJIKATA, M
    OOTSUYAMA, Y
    NAKAGAWA, M
    OHKOSHI, S
    SUGIMURA, T
    SHIMOTOHNO, K
    [J]. PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1990, 87 (24) : 9524 - 9528
  • [10] Identification of residues in the hepatitis C virus core protein that are critical for capsid assembly in a cell-free system
    Klein, KC
    Dellos, SR
    Lingappa, JR
    [J]. JOURNAL OF VIROLOGY, 2005, 79 (11) : 6814 - 6826