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去泛素化酶OTUD1通过调控宿主限制因子BST-2影响HIV-1释放。

The Deubiquitinase OTUD1 Influences HIV-1 Release by Regulating the Host Restriction Factor BST-2.

作者信息

Zhang Man-Di, Chen Fan, He Wen-Qiang, Lu Ying, Liu Feng-Liang, Zhang Hong-Guang, Yang Liu-Meng, Dong Chun-Sheng, Xiong Si-Dong, Zheng Yong-Tang

机构信息

State Key Laboratory of Genetic Evolution & Animal Models, Key Laboratory of Bioactive Peptides of Yunnan Province, KIZ-CUHK Joint Laboratory of Bioresources and Molecular Research in Common Diseases, Center for Biosafety Mega-Science, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming 650223, China.

KIZ-SU Joint Laboratory of Animal Model and Drug Development, College of Pharmaceutical Sciences, Soochow University, Suzhou 215021, China.

出版信息

Viruses. 2025 Feb 14;17(2):260. doi: 10.3390/v17020260.

DOI:10.3390/v17020260
PMID:40007014
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11860778/
Abstract

Bone marrow stromal cell antigen 2 (BST-2) is a restriction factor for human immunodeficiency virus type I (HIV-1) and plays an important role in regulating the release of viral particles. However, the antiviral efficacy of BST-2 is antagonized by the HIV-1-encoded accessory protein Vpu, which facilitates the degradation of BST-2 by recruiting E3 ubiquitin ligase β-TrCP. The involvement of deubiquitinases (DUBs) in counteracting BST-2 ubiquitination and influencing its stability during HIV-1 infection remains inadequately explored. In this study, we conducted a small interfering RNA (siRNA) screening of human DUBs and determined that OTUD1 interacts with BST-2, leading to a reduction in its K48- and K63-linked ubiquitination. This reduction increases BST-2 protein stability, and subsequently inhibits HIV-1 release. Our findings reveal a novel regulatory mechanism by which DUBs influence the stability of the HIV-1 restriction factor BST-2 to dampen viral release, providing a potential therapeutic target for HIV-1 antiviral intervention.

摘要

骨髓基质细胞抗原2（BST-2）是I型人类免疫缺陷病毒（HIV-1）的限制因子，在调节病毒颗粒释放中起重要作用。然而，HIV-1编码的辅助蛋白Vpu可拮抗BST-2的抗病毒功效，Vpu通过募集E3泛素连接酶β-TrCP促进BST-2的降解。在HIV-1感染期间，去泛素化酶（DUBs）在对抗BST-2泛素化并影响其稳定性方面的作用仍未得到充分研究。在本研究中，我们对人类DUBs进行了小干扰RNA（siRNA）筛选，并确定OTUD1与BST-2相互作用，导致其K48和K63连接的泛素化减少。这种减少增加了BST-2蛋白的稳定性，随后抑制了HIV-1的释放。我们的研究结果揭示了一种新的调节机制，即DUBs通过影响HIV-1限制因子BST-2的稳定性来抑制病毒释放，为HIV-1抗病毒干预提供了一个潜在的治疗靶点。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8a1e/11860778/32c917eb3430/viruses-17-00260-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8a1e/11860778/c553558725bb/viruses-17-00260-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8a1e/11860778/24cfa62f8820/viruses-17-00260-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8a1e/11860778/a4548b82f5c2/viruses-17-00260-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8a1e/11860778/32c917eb3430/viruses-17-00260-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8a1e/11860778/c553558725bb/viruses-17-00260-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8a1e/11860778/24cfa62f8820/viruses-17-00260-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8a1e/11860778/a4548b82f5c2/viruses-17-00260-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8a1e/11860778/32c917eb3430/viruses-17-00260-g005.jpg

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