The Deubiquitinase OTUD1 Influences HIV-1 Release by Regulating the Host Restriction Factor BST-2
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 facil...
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2025-02-01
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| Series: | Viruses |
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| Online Access: | https://www.mdpi.com/1999-4915/17/2/260 |
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| author | 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 |
| author_facet | 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 |
| author_sort | Man-Di Zhang |
| collection | DOAJ |
| description | 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. |
| format | Article |
| id | doaj-art-b6fb50626aea41b59303eca2fbd3a125 |
| institution | DOAJ |
| issn | 1999-4915 |
| language | English |
| publishDate | 2025-02-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Viruses |
| spelling | doaj-art-b6fb50626aea41b59303eca2fbd3a1252025-08-20T02:45:42ZengMDPI AGViruses1999-49152025-02-0117226010.3390/v17020260The Deubiquitinase OTUD1 Influences HIV-1 Release by Regulating the Host Restriction Factor BST-2Man-Di Zhang0Fan Chen1Wen-Qiang He2Ying Lu3Feng-Liang Liu4Hong-Guang Zhang5Liu-Meng Yang6Chun-Sheng Dong7Si-Dong Xiong8Yong-Tang Zheng9State 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, ChinaKIZ-SU Joint Laboratory of Animal Model and Drug Development, College of Pharmaceutical Sciences, Soochow University, Suzhou 215021, ChinaState 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, ChinaState 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, ChinaState 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, ChinaJiangsu Key Laboratory of Infection and Immunity, Institutes of Biology and Medical Sciences, Soochow University, Suzhou 215021, ChinaState 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, ChinaJiangsu Key Laboratory of Infection and Immunity, Institutes of Biology and Medical Sciences, Soochow University, Suzhou 215021, ChinaKIZ-SU Joint Laboratory of Animal Model and Drug Development, College of Pharmaceutical Sciences, Soochow University, Suzhou 215021, ChinaState 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, ChinaBone 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.https://www.mdpi.com/1999-4915/17/2/260deubiquitinaseOTUD1BST-2HIV-1 |
| spellingShingle | 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 The Deubiquitinase OTUD1 Influences HIV-1 Release by Regulating the Host Restriction Factor BST-2 Viruses deubiquitinase OTUD1 BST-2 HIV-1 |
| title | The Deubiquitinase OTUD1 Influences HIV-1 Release by Regulating the Host Restriction Factor BST-2 |
| title_full | The Deubiquitinase OTUD1 Influences HIV-1 Release by Regulating the Host Restriction Factor BST-2 |
| title_fullStr | The Deubiquitinase OTUD1 Influences HIV-1 Release by Regulating the Host Restriction Factor BST-2 |
| title_full_unstemmed | The Deubiquitinase OTUD1 Influences HIV-1 Release by Regulating the Host Restriction Factor BST-2 |
| title_short | The Deubiquitinase OTUD1 Influences HIV-1 Release by Regulating the Host Restriction Factor BST-2 |
| title_sort | deubiquitinase otud1 influences hiv 1 release by regulating the host restriction factor bst 2 |
| topic | deubiquitinase OTUD1 BST-2 HIV-1 |
| url | https://www.mdpi.com/1999-4915/17/2/260 |
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