Dengue Virus-Induced Autophagy Regulates Lipid Metabolism

Heaton, N. S. and Randall, G.

Cell Host & Microbe, 8, 422-432, 2010

Speaker：Siao-Fen Yeh (葉曉芬)                                 Time：14:10~15:00, April 13, 2011

Commentator：Dr. Jyh-Wei Shin (辛致煒老師)          Place：Room 601

Abstract

Autophagy may influence innate/adaptive immunity against intracellular pathogens. Some viruses use components of the autophagic machinery for their robust replication (1). Dengue virus (DV) infection induces autophagy, which further enhances DV replication and the release of viral particles. However, the mechanism of autophagy in DV infection is unclear. Recent study revealed that lipid droplets are associated with autophagic components during starvation, and inhibition on autophagy leads to the increase of triglyceride (TG) storage in lipid droplets (2). DV capsid protein and nonstructural protein 3 are associated with lipid droplets modification and fatty acid synthesis (3). The authors demonstrated that DV-induced autophagy regulates cellular lipid metabolism. Immunofluorescent assay showed that DV infection induced autophagy, and autophagy was associated with lipid droplets. DV-induced autophagy only decreased the area not the number of lipid droplet. The authors also demonstrated that lipid droplets participate in autophagosomal maturation. DV infection increased the ratio of lipid droplets delivering to lysosomes in an autophagy-dependent manner. TG, a component of lipid droplets, was depleted in DV-infected cells. The authors also revealed that addition of free fatty acid in the supernatant increased the titer of released viral particles with Atg gene knot-down groups or 3-MA treatment groups. In conclusion, the authors revealed that DV-induced autophagy enhances viral replication by regulating lipid metabolism of host cells, and this regulation could provide energy for viral biological functions.

References

1.          Lee, Y. R. et al. (2008) Autophagy machinery activated by dengue virus enhances virus replication. Virology 374, 240-248

2.          Singh, R. et al. (2009) Autophagy regulates lipid metabolism. Nature 458, 1131-1135.

3.          Heaton, N. S. et al. (2010) Dengue virus nonstructural protein 3 redistributes fatty acid synthase to sites of viral replication and increases cellular fatty acid synthesis. PNAS 107, 17345-17350.