Letter abstract
Nature Cell Biology 9, 1089 - 1097 (2007)
Published online: 26 August 2007 | doi:10.1038/ncb1631
There is an Erratum (October 2007) associated with this Letter.
The lipid droplet is an important organelle for hepatitis C virus production
Yusuke Miyanari1,2, Kimie Atsuzawa3, Nobuteru Usuda3, Koichi Watashi1,2, Takayuki Hishiki1,2, Margarita Zayas4, Ralf Bartenschlager4, Takaji Wakita5, Makoto Hijikata1,2 & Kunitada Shimotohno1,2,6
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, 2, 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 diseases4. HCV capsid protein (Core) associates with the LD5, envelope proteins E1 and E2 reside in the ER lumen6, 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.
- Department of Viral Oncology, Institute for Virus Research, Kyoto University, Kyoto 606-8507, Japan
- Graduate School of Biostudies, Kyoto University, Kyoto 606-8507, Japan
- Department of Anatomy, Fujita Health University School of Medicine, Toyoake 470-1192, Japan
- Department of Molecular Virology, University of Heidelberg, 69120 Heidelberg, Germany
- Department of Virology II, National Institute of Infectious Diseases, Tokyo 162-8640, Japan
- Correspondence should be addressed to K.S. (e-mail: e-mail: shimkuni@z8.keio.jp)
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