The lipid droplet is an important organelle for hepatitis C virus production (original) (raw)

Nature Cell Biology volume 9, pages 1089–1097 (2007)Cite this article

An Erratum to this article was published on 01 October 2007

Abstract

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.

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Acknowledgements

We thank T. Fujimoto and Y. Ohsaki at Nagoya University for helpful discussions and technical assistance. Y.M. is a recipient of a JSPS fellowship. K.S. is supported by Grants-in-Aid for cancer research and for the second-term comprehensive 10-year strategy for cancer control from the Ministry of Health, Labour and Welfare, as well as by a Grant-in-Aid for Scientific Research on Priority Areas “Integrative Research Toward the Conquest of Cancer” from the Ministry of Education, Culture, Sports, Science and Technology of Japan. T.W. is also supported, in part, by a Grant-in-Aid for Scientific Research from the Japan Society for the Promotion of Science; and by the Research on Health Sciences Focusing on Drug Innovation from the Japan Health Sciences Foundation. R.B. is supported by the Sonderforschungsbereich 638 (Teilprojekt A5) and the Deutsche Forschungsgemeinschaft (BA1505/2-1). M.Z. and R.B. thank the Nikon Imaging Center at the University of Heidelberg for providing access to their confocal fluorescence microscopes and Ulrike Engel for the excellent support.

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Authors and Affiliations

  1. Department of Viral Oncology, Institute for Virus Research, Kyoto University, Kyoto, 606-8507, Japan
    Yusuke Miyanari, Koichi Watashi, Takayuki Hishiki, Makoto Hijikata & Kunitada Shimotohno
  2. Graduate School of Biostudies, Kyoto University, Kyoto, 606-8507, Japan
    Yusuke Miyanari, Koichi Watashi, Takayuki Hishiki, Makoto Hijikata & Kunitada Shimotohno
  3. Department of Anatomy, Fujita Health University School of Medicine, Toyoake, 470-1192, Japan
    Kimie Atsuzawa & Nobuteru Usuda
  4. Department of Molecular Virology, University of Heidelberg, 69120, Heidelberg, Germany
    Margarita Zayas & Ralf Bartenschlager
  5. Department of Virology II, National Institute of Infectious Diseases, Tokyo, 162-8640, Japan
    Takaji Wakita
  6. Correspondence should be addressed to K.S. (e-mail: ),
    Kunitada Shimotohno

Authors

  1. Yusuke Miyanari
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  2. Kimie Atsuzawa
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  3. Nobuteru Usuda
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  4. Koichi Watashi
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  5. Takayuki Hishiki
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  6. Margarita Zayas
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  7. Ralf Bartenschlager
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  8. Takaji Wakita
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  9. Makoto Hijikata
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  10. Kunitada Shimotohno
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Contributions

Y.M. and K.S. planned experiments and analyses. Y.M. was responsible for experiments for Figs 1, 2, 3a–c, 4a–e and 5b. K.A., N.U., electron microscopy; T.H., Fig. 1e; M.Z., R.B., Fig. S2e; and K.S. and K.W., Fig. 4f–g. T.W. provided JFH1 strain. Y.M. and K.S. wrote the manuscript. All authors discussed the results and commented on the manuscript.

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Supplementary Figures 1, 2, 3, 4, 5 and 6, Supplementary Table, Supplementary Materials and Methods (PDF 2664 kb)

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Miyanari, Y., Atsuzawa, K., Usuda, N. et al. The lipid droplet is an important organelle for hepatitis C virus production.Nat Cell Biol 9, 1089–1097 (2007). https://doi.org/10.1038/ncb1631

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