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ISG15-蛋白酶USP18 是HIV-1复制的类增强剂

Chaohui Lin¹, Edmund Osei Kuffour¹, Taolan Li¹

¹Clinic of Gastroenterology, Hepatology and Infectious Diseases, Medical Faculty, Heinrich Heine University Düsseldorf, 40225 Düsseldorf, Germany.

|April 27, 2024

概括

人类USP18蛋白通过阻断p21和ISG15等抗病毒因子来帮助HIV-1复制,同时也抑制病毒DNA传感途径. 这表明USP18是抗病毒疗法的关键目标.

科学领域:

病毒学病毒学
免疫学免疫学免疫学
分子生物学分子生物学

背景情况:

干扰素 (IFN) 诱导的限制因子,包括ISG15,p21和SAMHD1,对于对病毒的先天免疫反应至关重要.
特定于ISG15的蛋白酶USP18可以抑制IFN的产生,而HIV-1可能会利用这一点来逃避免疫监测.

研究的目的:

研究USP18在HIV-1复制中的作用及其与宿主抗病毒因子的相互作用.
阐明USP18增强病毒复制并干扰免疫传感途径的机制.

主要方法:

在HIV-1感染期间USP18表达的分析.
评估p21抗病毒功能和p53活性.
研究新的dNTP生物合成途径和SAMHD1活性.
对cGAS-STING通路激活和STING ISGylation的评估.

主要成果:

艾滋病毒-1感染诱导USP18,通过废除p21的抗病毒功能来增强病毒复制.
USP18导致错误折叠的p53的积累,使野生类型的p53失活,并提高dNTP生物合成的调节,从而使SAMHD1.1失活.
尽管病毒DNA增加了,但USP18取消了cGAS-STING介导的病毒DNA传感,ISG15对这种传感至关重要.
在特定的残留物 (K224,K236,K289,K347,K338,K370) 上的STING ISGylation对于其寡合化和IFN诱导至关重要,K289 ISGylation的抑制抑制了这些过程.

结论:

人类USP18是一种新的因素,通过多种机制显著促进HIV-1复制.
USP18破坏了关键的抗病毒途径,包括p21功能和STING介导的免疫传感,成为潜在的治疗目标.

关键词:

艾滋病病毒-1 艾滋病病毒-1 在ISG15中,我们可以看到ISG15.在ISGylation中进行化.在SAMHD1中,我们可以使用SAMHD1.刺痛是一种刺痛.USP18 美元在 p53 里,p53 是一个 p53 号码.

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