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Codon-usage-based inhibition of HIV protein synthesis by human schlafen 11

机译:基于密码子的人schlafen 11对HIV蛋白合成的抑制

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摘要

In mammals, one of the most pronounced consequences of viral infection is the induction of type I interferons, cytokines with potent antiviral activity. Schlafen (Slfn) genes are a subset of interferon-stimulated early response genes (ISGs) that are also induced directly by pathogens via the interferon regulatory factor 3 (IRF3) pathway1. However, many ISGs are of unknown or incompletely understood function. Here we show that human SLFN 11 potently and specifically abrogates the production of retroviruses such as human immunodeficiency virus 1 (HIV-1). Our study revealed that SLFN 11 has no effect on the early steps of the retroviral infection cycle, including reverse transcription, integration and transcription. Rather, SLFN11 acts at the late stage of virus production by selectively inhibiting the expression of viral proteins in a codon-usage-dependent manner. We further find that SLFN11 binds transfer RNA, and counteracts changes in the tRNA pool elicited by the presence of HIV. Our studies identified a novel antiviral mechanism within the innate immune response, in which SLFN11 selectively inhibits viral protein synthesis in HIV-infected cells by means of codon-bias discrimination.
机译:在哺乳动物中,病毒感染的最明显后果之一是诱导I型干扰素,即具有有效抗病毒活性的细胞因子。 Schlafen(Slfn)基因是干扰素刺激的早期反应基因(ISG)的子集,ISGs也由病原体通过干扰素调节因子3(IRF3)途径直接诱导。但是,许多ISG的功能未知或不完全了解。在这里,我们显示了人类SLFN 11能有效地,特异性地消除诸如人类免疫缺陷病毒1(HIV-1)等逆转录病毒的产生。我们的研究表明SLFN 11对逆转录病毒感染周期的早期步骤没有影响,包括逆转录,整合和转录。而是,SLFN11通过以密码子使用依赖的方式选择性抑制病毒蛋白的表达,从而在病毒生产的后期发挥作用。我们进一步发现SLFN11结合转移RNA,并抵消了HIV存在引起的tRNA库的变化。我们的研究在先天免疫应答中发现了一种新的抗病毒机制,其中SLFN11通过密码子偏倚选择性地抑制HIV感染细胞中的病毒蛋白合成。

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  • 来源
    《Nature》 |2012年第7422期|p.125-128|共4页
  • 作者单位

    Section of Molecular Biology, Division of Biological Sciences, University of California San Diego, La Jotla, California 92093, USA;

    Section of Molecular Biology, Division of Biological Sciences, University of California San Diego, La Jotla, California 92093, USA;

    Section of Molecular Biology, Division of Biological Sciences, University of California San Diego, La Jotla, California 92093, USA;

    Section of Molecular Biology, Division of Biological Sciences, University of California San Diego, La Jotla, California 92093, USA;

    Section of Molecular Biology, Division of Biological Sciences, University of California San Diego, La Jotla, California 92093, USA;

    Departmentof Biochemistry and Molecular Biology, University of Chicago, Chicago, Illinois 60637, USA;

    Departmentof Biochemistry and Molecular Biology, University of Chicago, Chicago, Illinois 60637, USA;

    Laboratory of Genetics, The Salk Institute for Biological Studies, La Jolla, California 92037, USA;

    Departmentof Biochemistry and Molecular Biology, University of Chicago, Chicago, Illinois 60637, USA;

    Laboratory of Genetics, The Salk Institute for Biological Studies, La Jolla, California 92037, USA;

    Section of Molecular Biology, Division of Biological Sciences, University of California San Diego, La Jotla, California 92093, USA,Moores Cancer Center, University of California San Diego, La Jolla, California 92093, 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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