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首页> 外文期刊>Proceedings of the National Academy of Sciences of the United States of America >The antiviral protein, viperin, localizes to lipid droplets via its N-terminal amphipathic α-helix
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The antiviral protein, viperin, localizes to lipid droplets via its N-terminal amphipathic α-helix

机译：抗病毒蛋白viperin通过其N末端两亲性α-螺旋定位在脂质滴中

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摘要

Lipid droplets are intracellular lipid-storage organelles that are thought to be derived from the endoplasmic reticulum (ER). Several pathogens, notably hepatitis C virus, use lipid droplets for replication. Numerous questions remain about how lipid droplets are generated and used by viruses. Here we show that the IFN-induced antiviral protein viperin, which localizes to the cytosolic face of the ER and inhibits HCV, localizes to lipid droplets. We show that the N-terminal amphipathic a-helix of viperin that is responsible for ER localization is also necessary and sufficient to localize both viperin and the fluorescent protein dsRed to lipid droplets. Point mutations in the α-helix that prevent ER association also disrupt lipid droplet association, and sequential deletion mutants indicate that the same number of helical turns are necessary for ER and lipid droplet association. Finally, we show that the N-terminal amphipathic α-helix of the hepatitis C viral protein NS5A can localize dsRed and viperin to lipid droplets. These findings indicate that the amphipathic α-helices of viperin and NS5A are lipid droplet-targeting domains and suggest that viperin inhibits HCV by localizing to lipid droplets using a domain and mechanism similar to that used by HCV itself.
机译：脂质小滴是细胞内的脂质存储细胞器，被认为源自内质网（ER）。几种病原体，特别是丙型肝炎病毒，使用脂质滴进行复制。关于病毒如何产生和使用脂质滴，仍然存在许多问题。在这里，我们显示了IFN诱导的抗病毒蛋白viperin定位于脂质滴，该蛋白定位于ER的胞质表面并抑制HCV。我们显示负责ER定位的毒蛇素的N末端两亲性a螺旋也是必要的，也足以将毒蛇素和荧光蛋白dsRed定位到脂质液滴。阻止ER缔合的α螺旋中的点突变也破坏了脂滴缔合，顺序缺失突变体表明ER和脂滴缔合需要相同数量的螺旋圈数。最后，我们表明丙型肝炎病毒蛋白NS5A的N末端两亲性α-螺旋可以将dsRed和viperin定位于脂质滴。这些发现表明，viperin和NS5A的两亲性α螺旋是靶向脂质滴的域，并表明viperin通过使用类似于HCV本身的域和机制定位于脂质滴来抑制HCV。

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  • 作者

    Ella R. Hinson; Peter Cresswell;

  • 作者单位

    Department of Immunobiology, Yale University School of Medicine, New Haven, CT 06520-8011;

    Department of Immunobiology, Yale University School of Medicine, New Haven, CT 06520-8011 Howard Hughes Medical Institute, Yale University School of Medicine, New Haven, CT 06520-8011;

  • 收录信息 美国《科学引文索引》(SCI);美国《生物学医学文摘》(MEDLINE);美国《化学文摘》(CA);
  • 原文格式 PDF
  • 正文语种 eng
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  • 关键词

    HCV; NS5A;

    机译：丙型肝炎病毒;NS5A;

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