The Deubiquitinase OTUD1 Influences HIV-1 Release by Regulating the Host Restriction Factor BST-2
Man-Di Zhang,
Fan Chen,
Wen-Qiang He,
Ying Lu,
Feng-Liang Liu,
Hong-Guang Zhang,
Liu-Meng Yang,
Chun-Sheng Dong,
Si-Dong Xiong,
Yong-Tang Zheng
Affiliations
Man-Di Zhang
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
Fan Chen
KIZ-SU Joint Laboratory of Animal Model and Drug Development, College of Pharmaceutical Sciences, Soochow University, Suzhou 215021, China
Wen-Qiang He
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
Ying Lu
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
Feng-Liang Liu
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
Hong-Guang Zhang
Jiangsu Key Laboratory of Infection and Immunity, Institutes of Biology and Medical Sciences, Soochow University, Suzhou 215021, China
Liu-Meng Yang
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
Chun-Sheng Dong
Jiangsu Key Laboratory of Infection and Immunity, Institutes of Biology and Medical Sciences, Soochow University, Suzhou 215021, China
Si-Dong Xiong
KIZ-SU Joint Laboratory of Animal Model and Drug Development, College of Pharmaceutical Sciences, Soochow University, Suzhou 215021, China
Yong-Tang Zheng
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
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.
