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

An Erratum to this article was published on 01 October 2007


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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Figure 1: Core recruits NS proteins to LDs.
Figure 2: Core-dependent recruitment of active HCV replication complexes to the LD.
Figure 3: Spatial distribution of Core and NS5A relative to the LD.
Figure 4: LD associations of Core and NS proteins are necessary for the production of infectious HCV particles.
Figure 5: Virus-assembly takes place around the LDs.

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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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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).

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