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首页> 外文期刊>Biochemistry >The HIV gp41 Fusion Protein Inhibits T-Cell Activation through the Lentiviral Lytic Peptide 2 Motif
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The HIV gp41 Fusion Protein Inhibits T-Cell Activation through the Lentiviral Lytic Peptide 2 Motif

机译：HIV GP41融合蛋白通过慢病毒裂解肽2个基序抑制T细胞活化

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摘要

The human immunodeficiency virus enters its host cells by membrane fusion, initiated by the gp41 subunit of its envelope protein. gp41 has also been shown to bind T-cell receptor (TCR) complex components, interfering with TCR signaling leading to reduced T-cell activation. This immunoinhibitory activity is suggested to occur during the membrane fusion process and is attributed to various membranotropic regions of the gp41 ectodomain and to the transmembrane domain. Although extensively studied, the cytosolic region of gp41, termed the cytoplasmic tail (CT), has not been examined in the context of immune suppression. Here we investigated whether the CT inhibits T-cell activation in different T-cell models by utilizing gp41-derived peptides and expressed full gp41 proteins. We found that a conserved region of the CT, termed lentiviral lytic peptide 2 (LLP2), specifically inhibits the activation of mouse, Jurkat, and human primary T-cells. This inhibition resulted in reduced T-cell proliferation, gene expression, cytokine secretion, and cell surface expression of CD69. Differential activation of the TCR signaling cascade revealed that CT-based immune suppression occurs downstream of the TCR complex. Moreover, LLP2 peptide treatment of Jurkat and primary human T-cells impaired Akt but not NF kappa B and ERK1/2 activation, suggesting that immune suppression occurs through the Akt pathway. These findings identify a novel gp41 T-cell suppressive element with a unique inhibitory mechanism that can take place post-membrane fusion.
机译：人的免疫缺陷病毒通过膜融合进入其宿主细胞，由其包络蛋白的GP41亚基引发。还已显示GP41结合T细胞受体（TCR）复杂组分，干扰TCR信号，导致T细胞活化降低。建议在膜融合过程中发生这种免疫抑制活性，并且归因于GP41胞外域和跨膜结构域的各种膜熵区域。尽管广泛研究，但在免疫抑制的情况下，尚未检查GP41的细胞骨区域称为细胞质尾（CT）。在这里，我们通过利用GP41衍生的肽来研究CT是否抑制不同T细胞模型中的T细胞活化并表达全GP41蛋白。我们发现CT的保守区域称为慢病毒裂解肽2（LLP2），特异性抑制小鼠，Jurkat和人母原发性T细胞的活化。该抑制导致CD69的T细胞增殖，基因表达，细胞因子分泌和细胞表面表达降低。 TCR信号级联的差异激活表明，基于CT的免疫抑制发生在TCR复合物的下游。此外，LLP2肽治疗Jurkat和原发性人T细胞受损AKT但不是NF Kappa B和ERK1 / 2活化，表明免疫抑制通过AKT途径发生。这些发现鉴定了一种新的GP41 T细胞抑制元件，其具有可以发生膜融合的独特抑制机制。

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  • 来源
    《Biochemistry》 |2019年第6期|共15页
  • 作者

    Klug Yoel A.; Schwarzer Roland; Rotem Etai; Charni Meital; Nudelman Alon; Gramatica Andrea; Zarmi Batya; Rotter Varda; Shai Yechiel;

  • 作者单位

    Weizmann Inst Sci Dept Biomol Sci IL-7610001 Rehovot Israel;

    Univ Calif San Francisco Gladstone Inst Virol &

    Immunol San Francisco CA 94158 USA;

    Weizmann Inst Sci Dept Biomol Sci IL-7610001 Rehovot Israel;

    Weizmann Inst Sci Dept Mol Cell Biol IL-7610001 Rehovot Israel;

    Weizmann Inst Sci Dept Biomol Sci IL-7610001 Rehovot Israel;

    Univ Calif San Francisco Gladstone Inst Virol &

    Immunol San Francisco CA 94158 USA;

    Weizmann Inst Sci Dept Biomol Sci IL-7610001 Rehovot Israel;

    Weizmann Inst Sci Dept Mol Cell Biol IL-7610001 Rehovot Israel;

    Weizmann Inst Sci Dept Biomol Sci IL-7610001 Rehovot Israel;

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  • 正文语种 eng
  • 中图分类 生物化学;
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