SARS-CoV-2, HIV, and HPV: Convergent evolution of selective regulation of cGAS-STING signaling.

SARS-CoV-2, HIV, and HPV: Convergent evolution of selective regulation of cGAS-STING signaling.
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SARS-CoV-2、HIV 和 HPV:cGAS-STING 信号传导选择性调节的趋同进化

DOI:
10.1002/jmv.28220
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发表时间:
2023-01
影响因子:
12.7
通讯作者:
Yu, Xiao-Fang
Yu, Xiao-Fang
中科院分区:
医学3区
文献类型:
--
作者:
Shen, Si;Rui, Yajuan;Wang, Yanpu;Su, Jiaming;Yu, Xiao-Fang

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识别异常细胞质双链DNA并刺激先天免疫对于宿主防御病毒和肿瘤至关重要。环GMP-AMP(cGAMP)合酶(cGAS)是一种细胞溶质DNA传感器,可合成第二信使2′3′-cGAMP,随后激活干扰素基因刺激因子(STING)介导的TANK结合激酶1(TBK 1)/干扰素调节因子3(IRF 3)激活和I型干扰素(IFN-I)产生。cGAS-STING-介导的IFN-I抗病毒防御和由不同病毒开发的对策都已被广泛研究。然而,最近的研究揭示了严重急性呼吸综合征冠状病毒2型和人类免疫缺陷病毒(HIV)病毒蛋白在选择性调节cGAS-STING-介导的核因子-κB(NF-κB)信号传导方面的趋同进化特征,而对cGAS-STING-介导的TBK 1/IRF 3激活和IFN产生无任何影响。这种cGAS-STING-介导的NF-κB-依赖性抗病毒作用的潜在有益作用,以及IFN-I在2019冠状病毒病和HIV感染发病机制中可能的有害作用,值得更多关注和未来研究。
Recognizing aberrant cytoplasmic double‐stranded DNA and stimulating innate immunity is essential for the host's defense against viruses and tumors. Cyclic GMP–AMP (cGAMP) synthase (cGAS) is a cytosolic DNA sensor that synthesizes the second messenger 2′3′‐cGAMP and subsequently activates stimulator of interferon genes (STING)‐mediated activation of TANK‐binding kinase 1 (TBK1)/interferon regulatory factor 3 (IRF3) and the production of type I interferon (IFN‐I). Both the cGAS–STING‐mediated IFN‐I antiviral defense and the countermeasures developed by diverse viruses have been extensively studied. However, recent studies have revealed a convergent evolutionary feature of severe acute respiratory syndrome coronavirus 2 and human immunodeficiency virus (HIV) viral proteins in terms of the selective regulation of cGAS–STING‐mediated nuclear factor‐κB (NF‐κB) signaling without any effect on cGAS–STING‐mediated TBK1/IRF3 activation and IFN production. The potential beneficial effect of this cGAS–STING‐mediated, NF‐κB‐dependent antiviral effect, and the possible detrimental effect of IFN‐I in the pathogenesis of coronavirus disease 2019 and HIV infection deserve more attention and future investigation.
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