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首页> 外文期刊>Proceedings of the National Academy of Sciences of the United States of America >Simian immunodeficiency virus envelope glycoprotein counteracts tetherin/BST-2/CD317 by intracellular sequestration
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Simian immunodeficiency virus envelope glycoprotein counteracts tetherin/BST-2/CD317 by intracellular sequestration

机译：猿猴免疫缺陷病毒包膜糖蛋白可通过细胞内螯合作用抵消tetherin / BST-2 / CD317

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摘要

Tetherin is an IFN-inducible restriction factor that inhibits HIV-1 particle release in the absence of the HIV-1 countermeasure, viral protein U (Vpu). Although ubiquitous in HIV-1 and simian immunodeficiency viruses from chimpanzees, greater spot nosed monkeys, mustached monkeys, and Mona monkeys, other primate lentiviruses do not encode a Vpu protein. Here we demonstrate that SIV from Tantalus monkeys (SIVtan) encodes an envelope glycoprotein (SIVtan Env) able to counteract tetherin from Tantalus monkeys, rhesus monkeys, sooty mangabeys, and humans, but not from pigs. We show that sensitivity to Vpu but not SIVtan Env can be transferred with the human tetherin transmembrane region. We also identify a mutation in the tetherin extracellular domain, which almost completely abolishes sensitivity of human tetherin to SIVtan Env without compromising antiviral activity or sensitivity to Vpu. SIVtan Env expression results in a reduction of surface tetherin, as well as reduction in tetherin co-localization with mature surface-associated virus. Immuno-electron microscopy reveals co-localization of SIVtan Env with tetherin in intracellular tubulo-vesicular structures, suggesting that tetherin is sequestered away from budding virions at the cell surface. Along with HIV-1 Vpu and SIV Nef, envelope glycoprotein is the third and most broadly active lentiviral-encoded tetherin countermeasure to be described. Our observations emphasize the importance of tetherin in protecting mammals against viral infection and suggest that HIV-1 Vpu inhibitors may select active envelope mutants.
机译：Tetherin是一种IFN诱导型限制性因子，可在没有HIV-1对策病毒蛋白U（Vpu）的情况下抑制HIV-1颗粒的释放。尽管在黑猩猩，大鼻猴，胡子猴和蒙娜猴中，HIV-1和猿猴免疫缺陷病毒普遍存在，但其他灵长类慢病毒不编码Vpu蛋白。在这里，我们证明了来自Tantalus猴子（SIVtan）的SIV编码一种包膜糖蛋白（SIVtan Env），该蛋白能够抵消来自Tantalus猴子，恒河猴，煤烟man和人的tetherin，但不能抵消来自猪的tetherin。我们表明对Vpu而不是SIVtan Env的敏感性可以与人系绳蛋白跨膜区转移。我们还发现在系膜蛋白胞外域中的突变，该突变几乎完全消除了人系膜蛋白对SIVtan Env的敏感性，而不会影响抗病毒活性或对Vpu的敏感性。 SIVtan Env的表达导致表面tetherin减少，以及与成熟的表面相关病毒共定位的tetherin减少。免疫电子显微镜检查显示SIVtan Env与Tetherin在细胞内微管泡结构中共定位，表明Tetherin与细胞表面的萌芽病毒体隔离。与HIV-1 Vpu和SIV Nef一起，包膜糖蛋白是描述的第三个也是最广泛的慢病毒编码系链蛋白对策。我们的观察结果强调了系缆素在保护哺乳动物免受病毒感染中的重要性，并暗示HIV-1 Vpu抑制剂可能会选择活性包膜突变体。

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    Ravindra K. Gupta; Petra Mlcochova; Annegret Pelchen-Matthews; Sarah J. Petit; Giada Mattiuzzo; Deenan Pillay; Yasuhiro Takeuchi; Mark Marsh; Greg J. Towers;

  • 作者单位

    Medical Research Council Centre for Medical Molecular Virology, Division of Infection and Immunity, University College London, 46 Cleveland Street, London W1T 4JF, United Kingdom;

    Cell Biology Unit, Medical Research Council Laboratory for Molecular Cell Biology, University College London, London WC1E 6BT, United Kingdom;

    Cell Biology Unit, Medical Research Council Laboratory for Molecular Cell Biology, University College London, London WC1E 6BT, United Kingdom;

    Medical Research Council Centre for Medical Molecular Virology, Division of Infection and Immunity, University College London, 46 Cleveland Street, London W1T 4JF, United Kingdom;

    Medical Research Council Centre for Medical Molecular Virology, Division of Infection and Immunity, University College London, 46 Cleveland Street, London W1T 4JF, United Kingdom;

    Medical Research Council Centre for Medical Molecular Virology, Division of Infection and Immunity, University College London, 46 Cleveland Street, London W1T 4JF, United Kingdom Centre for Infections, Health Protection Agency, 61 Colindale Ave, London NW9 2QT, United Kingdom;

    Medical Research Council Centre for Medical Molecular Virology, Division of Infection and Immunity, University College London, 46 Cleveland Street, London W1T 4JF, United Kingdom;

    Cell Biology Unit, Medical Research Council Laboratory for Molecular Cell Biology, University College London, London WC1E 6BT, United Kingdom;

    Medical Research Council Centre for Medical Molecular Virology, Division of Infection and Immunity, University College London, 46 Cleveland Street, London W1T 4JF, United Kingdom;

  • 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

    HIV; restriction; innate immunity;

    机译：艾滋病病毒;限制;先天免疫;

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