Department of Medical Microbiology, Radboud Institute for Molecular Life Sciences, Radboud University Medical Center, Nijmegen, The Netherlands.
Insect-Virus Interactions Group, Department of Genomes and Genetics, Institut Pasteur, Paris, France.
Sci Rep. 2019 Feb 14;9(1):2065. doi: 10.1038/s41598-019-38559-x.
The fruit fly Drosophila melanogaster is a valuable model organism for the discovery and characterization of innate immune pathways, but host responses to virus infection remain incompletely understood. Here, we describe a novel player in host defense, Sgroppino (Sgp). Genetic depletion of Sgroppino causes hypersensitivity of adult flies to infections with the RNA viruses Drosophila C virus, cricket paralysis virus, and Flock House virus. Canonical antiviral immune pathways are functional in Sgroppino mutants, suggesting that Sgroppino exerts its activity via an as yet uncharacterized process. We demonstrate that Sgroppino localizes to peroxisomes, organelles involved in lipid metabolism. In accordance, Sgroppino-deficient flies show a defect in lipid metabolism, reflected by higher triglyceride levels, higher body mass, and thicker abdominal fat tissue. In addition, knock-down of Pex3, an essential peroxisome biogenesis factor, increases sensitivity to virus infection. Together, our results establish a genetic link between the peroxisomal protein Sgroppino, fat metabolism, and resistance to virus infection.
果蝇 Drosophila melanogaster 是发现和鉴定固有免疫途径的一种有价值的模式生物，但宿主对病毒感染的反应仍不完全清楚。在这里，我们描述了一种宿主防御的新成员，Sgroppino（Sgp）。Sgroppino 的基因缺失会导致成年果蝇对 RNA 病毒果蝇 C 病毒、蟋蟀麻痹病毒和 Flock House 病毒的感染变得过度敏感。Sgroppino 突变体中经典的抗病毒免疫途径是功能性的，这表明 Sgroppino 通过尚未确定的过程发挥其活性。我们证明 Sgroppino 定位于过氧化物酶体，这是一种参与脂质代谢的细胞器。相应地，Sgroppino 缺陷型果蝇表现出脂质代谢缺陷，表现在甘油三酯水平升高、体重增加和腹部脂肪组织变厚。此外，必需的过氧化物体生物发生因子 Pex3 的敲低会增加对病毒感染的敏感性。总之，我们的结果在过氧化物体蛋白 Sgroppino、脂肪代谢和对病毒感染的抗性之间建立了遗传联系。
