Autophagy is an essential component of Drosophila immunity against vesicular stomatitis virus.

Autophagy is an essential component of Drosophila immunity against vesicular stomatitis virus.
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DOI:
10.1016/j.immuni.2009.02.009
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发表时间:
2009-04-17
期刊:
影响因子:
32.4
通讯作者:
Cherry, Sara
Cherry, Sara
中科院分区:
医学1区
文献类型:
--
作者:
Shelly, Spencer;Lukinova, Nina;Bambina, Shelly;Berman, Allison;Cherry, Sara

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内在的先天免疫机制是抵抗病原体的第一道防线,并且存在于受感染细胞中自主控制感染。在这里,我们发现自噬是一种可以降解细胞质成分的内在机制,在模式生物果蝇中对哺乳动物病毒病原体水泡性口炎病毒(VSV)发挥直接抗病毒作用。我们发现表面糖蛋白 VSVG 很可能是启动这种细胞自主反应的病原体相关分子模式 (PAMP)。一旦被激活,自噬就会减少病毒复制,而自噬的抑制会导致细胞和动物中病毒复制和发病机制的增加。最后,我们表明抗病毒反应是由磷脂酰肌醇 3-激酶 (PI3K)/Akt 信号通路控制的,该信号通路通常根据营养物质的可用性调节自噬。总而言之,这些数据揭示了一种内在的抗病毒程序,该程序将病毒识别与进化上保守的营养信号和自噬途径联系起来。
Intrinsic innate immune mechanisms are the first line of defense against pathogens, and exist to control infection autonomously in infected cells. Here we show that autophagy, an intrinsic mechanism that can degrade cytoplasmic components, plays a direct anti-viral role against the mammalian viral pathogen Vesicular Stomatitis Virus (VSV) in the model organism Drosophila. We found that the surface glycoprotein, VSVG, is likely the pathogen-associated molecular pattern (PAMP) that initiates this cell-autonomous response. Once activated, autophagy decreases viral replication, and repression of autophagy leads to increased viral replication and pathogenesis in cells and animals. Lastly, we show that the antiviral response is controlled by the phosphatidylinositol 3-kinase (PI3K)/Akt signaling pathway which normally regulates autophagy in response to nutrient availability. Altogether these data uncover an intrinsic antiviral program that that links viral recognition to the evolutionarily conserved nutrient signaling and autophagy pathways.
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