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

Miyanari, Y. et al. Nature Cell Biol. 9, 1089-1097 (2007)

Speaker: Po-Shun Wang (王柏舜)                                                 Time: 15:00-16:00, Dec. 5, 2007

Commentator: Dr. Kung-Chia Young (楊孔嘉老師)                               Place: Room 601

Abstract:

Hepatitis C virus (HCV) classified in the genus Hepacivirus within the family of Flaviviridae is the major cause of chronic liver diseases. The viral genome consists of a 9.6 kb single-stranded positive- sense RNA molecule encoding a precursor polyprotein of about 3000 amino acid residues. The polyprotein is cleaved both co- and post-translationally at the endoplasmic reticulum (ER) membrane by cellular and viral proteases to yield the mature structural and nonstructural (NS) proteins ⁽¹⁾. Core, one of the structural proteins, forms the viral capsid and is targeted to lipid droplets (LDs), which serve as intracellular neutral lipid storage organelles and dynamically move from the ER membrane to become an independent organelle that is bounded by a limiting monolayer of phospholipids and LD-associated proteins ⁽²⁾. The replication of HCV genome is compartmentalized by lipid membrane structure ⁽³⁾, however, how and where HCV particles are assembled, has not yet been elucidated in detail. Therefore, the aim of this study is to examine whether the LDs are involved in the multiplication of infectious virus particles. The authors clarified that Core recruits non-structural (NS) proteins as well as HCV replication complexes to the LD-associated membranes, also named ER-derived bilayer membranes, and this association of HCV proteins with LDs is essential for producing infectious viruses. Moreover, they proposed a model by which HCV assembly occurs in close proximity to LDs, suggesting that LDs are the crucial element of the HCV assembly process. Taken together, the authors' findings demonstrate the novel function of LDs during infectious HCV replication, contribute to the understanding of HCV life cycle, and offer profound inspiration on developing new access for antiviral strategies.

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