Autophagy Is an Essential Component of Drosophila Immunity against Vesicular Stomatitis Virus

Shelly S., Lukinova N., Bambina S., Berman A. and Cherry S.

2009. Immunity 30(4): 588-98

Speaker: Hsuan-Yun Hu (胡瑄耘)                                        Time: 13:10~14:00, Sep. 30, 2009

Commentator: Dr. Chiou-Feng Lin (林秋烽博士)               Place: Room 601

Abstract:

        Autophagy is a process of cellular homeostasis. It executes the clearance of aggregated proteins, damaged organelles, and long-lived proteins in the cytoplasm. Numerous studies indicated that autophagy has regulatory and effector functions in innate and adaptive immunity [1]. In this paper, the authors reveal the role of autophagy in defense virus infections through innate immunity. Vesicular stomatitis virus (VSV) was used to infect Drosophila melanogaster (D. melanogaster) as a study model. VSV is a negative single strand RNA virus and belongs to Rhabdoviridae family. It infects both insects and mammls. D. melanogaster is genetically tractable and relies on innate immune system to combat pathogens [2]. Initially, the authors verified that VSV infection activated autophagy and affected virus replication in Drosophila S2 cells. To identify which component of VSV can induce autophagy, they found that VSV-G, the viral surface glycoprotein, is a pathogen-associated molecular pattern (PAMP), which was recognized by Drosophila cells and induced autophagy. In vivo study, they used the Gal4-UAS system to knockout autophagy related genes, atg18, atg7and atg12, and showed that VSV infection induced autophagy both in primary cells, larval hemocytes, and adult flies. Autophagy plays an antiviral role both in vivo and in vitro. Finally, the authors revealed that the PI3K-Akt pathway, which is known to negatively regulate autophagy during development and starvation, is inhibited by VSV and therefore autophagic activity was induced. Collectively, when VSV infected the flies, cells recognize the VSV-G by undetermined pattern recognized receptors. The nutrient-signaling pathway was attenuated and autophagy was induced, which is beneficial for host that to defense the virus replication.

References:

1.         Deretic, V., Multiple regulatory and effector roles of autophagy in immunity. Curr Opin Immunol, 2009. 21: 53-62.

2.         Lemaitre, B. and J. Hoffmann, The host defense of Drosophila melanogaster. Annu Rev Immunol, 2007. 25: 697-743.