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首页> 外文期刊>Nature >Cell death by pyroptosis drives CD4 T-cell depletion in HIV-1 infection
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Cell death by pyroptosis drives CD4 T-cell depletion in HIV-1 infection

机译：凋亡引起的细胞死亡在HIV-1感染中驱动CD4 T细胞耗竭

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摘要

CD4 T细胞（携带能够识别被病毒感染的细胞表面上的CD4抗原的受体的辅助T细胞)的丧失是艾滋病发病的根源。在这项研究中，Warner Greene等人识别出静止的淋巴CD4 T细胞在 HIV感染过程中被耗尽的机制。利用保持了天 然淋巴环境的人淋巴组织的体外培养，本文 作者发现，失败的病毒复制触发由"半胱天冬 酶-1"介导的细胞焦亡，后者造成细胞死亡。 "半胱天冬酶-1"抑制药物（它们在临床试验中已被发现是安全的）在体外能挽救细胞死亡， 这说明可能存在新的一类以主体、而不是以病毒为作用目标的抗艾滋病治疗药物。%The pathway causing CD4 T-cell death in HIV-infected hosts remains poorly understood although apoptosis has been proposed as a key mechanism. We now show that caspase-3-mediated apoptosis accounts for the death of only a small fraction of CD4 T cells corresponding to those that are both activated and productively infected. The remaining over 95% of quiescent lymphoid CD4 T cells die by caspase-1-mediated pyroptosis triggered by abortive viral infection. Pyroptosis corresponds to an intensely inflammatory form of programmed cell death in which cytoplasmic contents and pro-inflammatory cytokines, including IL-1β, are released. This death pathway thus links the two signature events in HIV infection-CD4 T-cell depletion and chronic inflammation-and creates a pathogenic vicious cycle in which dying CD4 T cells release inflammatory signals that attract more cells to die. This cycle can be broken by caspase 1 inhibitors shown to be safe in humans, raising the possibility of a new class of 'anti-AIDS' therapeutics targeting the host rather than the virus.
机译：CD4 T细胞（携带能够识别被病毒感染的细胞表面上的CD4抗原的受体的辅助T细胞)的丧失是艾滋病发病的根源。在这项研究中，Warner Greene等人识别出静止的淋巴CD4 T细胞在 HIV感染过程中被耗尽的机制。利用保持了天 然淋巴环境的人淋巴组织的体外培养，本文 作者发现，失败的病毒复制触发由"半胱天冬 酶-1"介导的细胞焦亡，后者造成细胞死亡。 "半胱天冬酶-1"抑制药物（它们在临床试验中已被发现是安全的）在体外能挽救细胞死亡， 这说明可能存在新的一类以主体、而不是以病毒为作用目标的抗艾滋病治疗药物。%The pathway causing CD4 T-cell death in HIV-infected hosts remains poorly understood although apoptosis has been proposed as a key mechanism. We now show that caspase-3-mediated apoptosis accounts for the death of only a small fraction of CD4 T cells corresponding to those that are both activated and productively infected. The remaining over 95% of quiescent lymphoid CD4 T cells die by caspase-1-mediated pyroptosis triggered by abortive viral infection. Pyroptosis corresponds to an intensely inflammatory form of programmed cell death in which cytoplasmic contents and pro-inflammatory cytokines, including IL-1β, are released. This death pathway thus links the two signature events in HIV infection-CD4 T-cell depletion and chronic inflammation-and creates a pathogenic vicious cycle in which dying CD4 T cells release inflammatory signals that attract more cells to die. This cycle can be broken by caspase 1 inhibitors shown to be safe in humans, raising the possibility of a new class of 'anti-AIDS' therapeutics targeting the host rather than the virus.

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  • 来源
    《Nature》 |2014年第7484期|509-514A3|共7页
  • 作者

    Gilad Doitsh; Nicole L. K. Galloway; Xin Geng; Zhiyuan Yang; Kathryn M. Monroe; Orlando Zepeda; Peter W. Hunt; Hiroyu Hatano; Stefanie Sowinski; Isa Munoz-Arias; Warner C. Greene;

  • 作者单位

    Gladstone Institute of Virology and Immunology, 1650 Owens Street, San Francisco, California 94158, USA;

    Gladstone Institute of Virology and Immunology, 1650 Owens Street, San Francisco, California 94158, USA;

    Gladstone Institute of Virology and Immunology, 1650 Owens Street, San Francisco, California 94158, USA;

    Gladstone Institute of Virology and Immunology, 1650 Owens Street, San Francisco, California 94158, USA;

    Gladstone Institute of Virology and Immunology, 1650 Owens Street, San Francisco, California 94158, USA;

    Gladstone Institute of Virology and Immunology, 1650 Owens Street, San Francisco, California 94158, USA;

    Department of Medicine, University of California, San Francisco, 505 Parnassus Avenue, SanFrancisco, California 94143, USA;

    Department of Medicine, University of California, San Francisco, 505 Parnassus Avenue, SanFrancisco, California 94143, USA;

    Gladstone Institute of Virology and Immunology, 1650 Owens Street, San Francisco, California 94158, USA;

    Gladstone Institute of Virology and Immunology, 1650 Owens Street, San Francisco, California 94158, USA;

    Gladstone Institute of Virology and Immunology, 1650 Owens Street, San Francisco, California 94158, USA,Department of Medicine, University of California, San Francisco, 505 Parnassus Avenue, SanFrancisco, California 94143, USA,Department of Microbiology and Immunology, University of California, San Francisco, 505 Parnassus Avenue, San Francisco, California 94143, USA;

  • 收录信息 美国《科学引文索引》(SCI);美国《工程索引》(EI);美国《生物学医学文摘》(MEDLINE);美国《化学文摘》(CA);
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