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泛素化和 SUMO 化在逆转录病毒感染和潜伏中的作用。

The Involvement of Ubiquitination and SUMOylation in Retroviruses Infection and Latency.

机构信息

State Key Laboratory of Respiratory Disease, Guangzhou Medical University, Guangzhou 511400, China.

Guangzhou Laboratory, Guangzhou International Bio-Island, Guangzhou 510005, China.

出版信息

Viruses. 2023 Apr 17;15(4):985. doi: 10.3390/v15040985.

Abstract

Retroviruses, especially the pathogenic human immunodeficiency virus type 1 (HIV-1), have severely threatened human health for decades. Retroviruses can form stable latent reservoirs via retroviral DNA integration into the host genome, and then be temporarily transcriptional silencing in infected cells, which makes retroviral infection incurable. Although many cellular restriction factors interfere with various steps of the life cycle of retroviruses and the formation of viral latency, viruses can utilize viral proteins or hijack cellular factors to evade intracellular immunity. Many post-translational modifications play key roles in the cross-talking between the cellular and viral proteins, which has greatly determined the fate of retroviral infection. Here, we reviewed recent advances in the regulation of ubiquitination and SUMOylation in the infection and latency of retroviruses, focusing on both host defense- and virus counterattack-related ubiquitination and SUMOylation system. We also summarized the development of ubiquitination- and SUMOylation-targeted anti-retroviral drugs and discussed their therapeutic potential. Manipulating ubiquitination or SUMOylation pathways by targeted drugs could be a promising strategy to achieve a "sterilizing cure" or "functional cure" of retroviral infection.

摘要

逆转录病毒,尤其是致病性的人类免疫缺陷病毒 1 型(HIV-1),几十年来严重威胁着人类健康。逆转录病毒可通过逆转录病毒 DNA 整合到宿主基因组中形成稳定的潜伏储库,然后在感染细胞中暂时转录沉默,从而使逆转录病毒感染无法治愈。尽管许多细胞限制因子干扰逆转录病毒生命周期的各个步骤和病毒潜伏的形成,但病毒可以利用病毒蛋白或劫持细胞因子来逃避细胞内免疫。许多翻译后修饰在细胞蛋白和病毒蛋白之间的交流中起着关键作用,这极大地决定了逆转录病毒感染的命运。在这里,我们综述了近年来在逆转录病毒感染和潜伏过程中泛素化和 SUMO 化修饰的调控作用,重点关注了宿主防御和病毒反击相关的泛素化和 SUMO 化系统。我们还总结了泛素化和 SUMO 化靶向抗逆转录病毒药物的发展,并讨论了它们的治疗潜力。通过靶向药物操纵泛素化或 SUMO 化途径可能是实现逆转录病毒感染“杀菌治愈”或“功能治愈”的有前途的策略。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f359/10144533/388d9143ac52/viruses-15-00985-g001.jpg

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