HIV-2/SIV Vpx targets a novel functional domain of STING to selectively inhibit cGAS-STING-mediated NF-κB signalling
HIV-2/SIV Vpx targets a novel functional domain of STING to selectively inhibit cGAS-STING-mediated NF-κB signalling
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HIV-2/SIV Vpx 靶向 STING 的一个新功能域，选择性抑制 cGAS-STING 介导的 NF-kappa B 信号传导
DOI：
10.1038/s41564-019-0585-4
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发表时间：
2019-12-01
影响因子：
28.3
通讯作者：
Yu, Xiao-Fang
中科院分区：
文献类型：
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作者：
Su, Jiaming;Rui, Yajuan;Yu, Xiao-Fang
先天免疫是宿主抵御病原体的第一道防线。先天免疫反应的抑制对于所有病毒的存活都是必不可少的。然而，先天免疫和艾滋病毒/SIV之间的相互作用只是很差的特点。我们已经发现Vpx作为一种新的先天免疫激活抑制剂，与STING信号体相关，并干扰NF-κ B的核转位和先天免疫基因的诱导。Vpx的这种新功能可以与其介导抗病毒因子SAMHD 1降解的作用分开，并且在不同的HIV-2/SIV Vpx中是保守的。Vpx选择性抑制cGAS-STING介导的核因子-κ B信号传导。此外，Vpx和Vpr对cGAS-STING活性具有互补活性。由于缺乏Vpx和Vpr的SIVMAC比Vpr或Vpx单独缺乏的SIV致病性低，因此HIV/SIV对先天免疫的抑制可能是关键的致病决定因素，使其成为有希望的干预靶点。
Innate immunity is the first line of host defence against pathogens. Suppression of innate immune responses is essential for the survival of all viruses. However, the interplay between innate immunity and HIV/SIV is only poorly characterized. We have discovered Vpx as a novel inhibitor of innate immune activation that associates with STING signalosomes and interferes with the nuclear translocation of NF-kappa B and the induction of innate immune genes. This new function of Vpx could be separated from its role in mediating degradation of the antiviral factor SAMHD1, and is conserved among diverse HIV-2/SIV Vpx. Vpx selectively suppressed cGAS-STING-mediated nuclear factor-kappa B signalling. Furthermore, Vpx and Vpr had complementary activities against cGAS-STING activity. Since SIVMAC lacking both Vpx and Vpr was less pathogenic than SIV deficient for Vpr or Vpx alone, suppression of innate immunity by HIV/SIV is probably a key pathogenic determinant, making it a promising target for intervention.