SAP30 deacetylates the Tas protein to inhibit PFV replication

Abstract Background Foamy viruses (FVs), a unique class of retroviruses, establish lifelong latent infections in the host without causing symptoms, contributing to the relatively slow progress in FV research. However, key mutations in FVs can result in severe consequences due to their broad cellular...

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Main Authors: Chenchen Wang, Junshi Zhang, Yali Xu, Jiawei Zhao, Manman Qiu, Xingli Zhao, Guoqiang Li, Wentao Qiao, Juan Tan
Format: Article
Language:English
Published: BMC 2025-04-01
Series:Cell & Bioscience
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Online Access:https://doi.org/10.1186/s13578-025-01400-2
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author Chenchen Wang
Junshi Zhang
Yali Xu
Jiawei Zhao
Manman Qiu
Xingli Zhao
Guoqiang Li
Wentao Qiao
Juan Tan
author_facet Chenchen Wang
Junshi Zhang
Yali Xu
Jiawei Zhao
Manman Qiu
Xingli Zhao
Guoqiang Li
Wentao Qiao
Juan Tan
author_sort Chenchen Wang
collection DOAJ
description Abstract Background Foamy viruses (FVs), a unique class of retroviruses, establish lifelong latent infections in the host without causing symptoms, contributing to the relatively slow progress in FV research. However, key mutations in FVs can result in severe consequences due to their broad cellular tropism, underscoring the importance of studying latent FV infections. Results To identify new host proteins involved in the replication of prototype foamy virus (PFV), we previously infected the human fibrosarcoma cell line HT1080 with PFV and performed transcriptomic sequencing. The analysis revealed a significant upregulation of SAP30 mRNA levels following PFV infection. Further experiments demonstrated that PFV infection enhances SAP30 promoter activity via the Tas protein, leading to increased SAP30 mRNA and protein expression. Overexpression of SAP30 inhibited PFV replication, whereas knockdown of endogenous SAP30 enhanced PFV replication. Furthermore, SAP30 interacted with the Tas protein to induce its deacetylation, thereby suppressing Tas-mediated transactivation of the PFV LTR and IP promoters. The Sin3 interaction domain at the C-terminus of SAP30 was identified as the critical domain for inhibiting PFV transcription. Conclusions Our findings suggest that SAP30 inhibits PFV replication by deacetylating the Tas protein, thereby disrupting its transcriptional activation function. Key words: prototype foamy virus; SAP30; Tas; transcription; deacetylation.
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spelling doaj-art-4d309445c8264b51b7c4888e1acc06212025-08-20T03:15:12ZengBMCCell & Bioscience2045-37012025-04-0115111210.1186/s13578-025-01400-2SAP30 deacetylates the Tas protein to inhibit PFV replicationChenchen Wang0Junshi Zhang1Yali Xu2Jiawei Zhao3Manman Qiu4Xingli Zhao5Guoqiang Li6Wentao Qiao7Juan Tan8Key Laboratory of Molecular Microbiology and Technology, College of Life Sciences, Ministry of Education, Nankai UniversityDepartment of Hematology, Oncology Center, Tianjin Union Medical Center, The First Affiliated Hospital of Nankai UniversityKey Laboratory of Molecular Microbiology and Technology, College of Life Sciences, Ministry of Education, Nankai UniversityKey Laboratory of Molecular Microbiology and Technology, College of Life Sciences, Ministry of Education, Nankai UniversityKey Laboratory of Molecular Microbiology and Technology, College of Life Sciences, Ministry of Education, Nankai UniversityDepartment of Hematology, Oncology Center, Tianjin Union Medical Center, The First Affiliated Hospital of Nankai UniversityKey Laboratory of Molecular Microbiology and Technology, College of Life Sciences, Ministry of Education, Nankai UniversityKey Laboratory of Molecular Microbiology and Technology, College of Life Sciences, Ministry of Education, Nankai UniversityKey Laboratory of Molecular Microbiology and Technology, College of Life Sciences, Ministry of Education, Nankai UniversityAbstract Background Foamy viruses (FVs), a unique class of retroviruses, establish lifelong latent infections in the host without causing symptoms, contributing to the relatively slow progress in FV research. However, key mutations in FVs can result in severe consequences due to their broad cellular tropism, underscoring the importance of studying latent FV infections. Results To identify new host proteins involved in the replication of prototype foamy virus (PFV), we previously infected the human fibrosarcoma cell line HT1080 with PFV and performed transcriptomic sequencing. The analysis revealed a significant upregulation of SAP30 mRNA levels following PFV infection. Further experiments demonstrated that PFV infection enhances SAP30 promoter activity via the Tas protein, leading to increased SAP30 mRNA and protein expression. Overexpression of SAP30 inhibited PFV replication, whereas knockdown of endogenous SAP30 enhanced PFV replication. Furthermore, SAP30 interacted with the Tas protein to induce its deacetylation, thereby suppressing Tas-mediated transactivation of the PFV LTR and IP promoters. The Sin3 interaction domain at the C-terminus of SAP30 was identified as the critical domain for inhibiting PFV transcription. Conclusions Our findings suggest that SAP30 inhibits PFV replication by deacetylating the Tas protein, thereby disrupting its transcriptional activation function. Key words: prototype foamy virus; SAP30; Tas; transcription; deacetylation.https://doi.org/10.1186/s13578-025-01400-2Prototype foamy virusSAP30TasTranscriptionDeacetylation
spellingShingle Chenchen Wang
Junshi Zhang
Yali Xu
Jiawei Zhao
Manman Qiu
Xingli Zhao
Guoqiang Li
Wentao Qiao
Juan Tan
SAP30 deacetylates the Tas protein to inhibit PFV replication
Cell & Bioscience
Prototype foamy virus
SAP30
Tas
Transcription
Deacetylation
title SAP30 deacetylates the Tas protein to inhibit PFV replication
title_full SAP30 deacetylates the Tas protein to inhibit PFV replication
title_fullStr SAP30 deacetylates the Tas protein to inhibit PFV replication
title_full_unstemmed SAP30 deacetylates the Tas protein to inhibit PFV replication
title_short SAP30 deacetylates the Tas protein to inhibit PFV replication
title_sort sap30 deacetylates the tas protein to inhibit pfv replication
topic Prototype foamy virus
SAP30
Tas
Transcription
Deacetylation
url https://doi.org/10.1186/s13578-025-01400-2
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AT jiaweizhao sap30deacetylatesthetasproteintoinhibitpfvreplication
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AT xinglizhao sap30deacetylatesthetasproteintoinhibitpfvreplication
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