PREB inhibits the replication of prototype foamy virus by affecting its transcription
Abstract Background Foamy viruses (FVs) are unique nonpathogenic retroviruses, which remain latent in the host for a long time. Therefore, they may be safe, effective gene transfer vectors. In this study, were assessed FV–host cell interactions and the molecular mechanisms underlying FV latent infec...
| Main Authors: | , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
BMC
2023-10-01
|
| Series: | Virology Journal |
| Subjects: | |
| Online Access: | https://doi.org/10.1186/s12985-023-02211-y |
| _version_ | 1797647388959047680 |
|---|---|
| author | Junshi Zhang Yali Xu Chenchen Wang Xiaopeng Tuo Xingli Zhao Wentao Qiao Juan Tan |
| author_facet | Junshi Zhang Yali Xu Chenchen Wang Xiaopeng Tuo Xingli Zhao Wentao Qiao Juan Tan |
| author_sort | Junshi Zhang |
| collection | DOAJ |
| description | Abstract Background Foamy viruses (FVs) are unique nonpathogenic retroviruses, which remain latent in the host for a long time. Therefore, they may be safe, effective gene transfer vectors. In this study, were assessed FV–host cell interactions and the molecular mechanisms underlying FV latent infection. Methods We used the prototype FV (PFV) to infect HT1080 cells and a PFV indicator cell line (PFVL) to measure virus titers. After 48 h of infection, the culture supernatant (i.e., cell-free PFV particles) and transfected cells (i.e., cell-associated PFV particles) were harvested and incubated with PFVL. After another 48 h, the luciferase activity was used to measure virus titers. Results Through transcriptomics sequencing, we found that PREB mRNA expression was significantly upregulated. Moreover, PREB overexpression reduced PFV replication, whereas endogenous PREB knockdown increased PFV replication. PREB interacted with the Tas DNA-binding and transcriptional activation domains and interfered with its binding to the PFV long terminal repeat and internal promoter, preventing the recruitment of transcription factors and thereby inhibiting the transactivation function of Tas. PREB C-terminal 329–418 aa played a major role in inhibiting PFV replication; PREB also inhibited bovine FV replication. Therefore, PREB has a broad-spectrum inhibitory effect on FV replication. Conclusions Our results demonstrated that PREB inhibits PFV replication by impeding its transcription. |
| first_indexed | 2024-03-11T15:15:36Z |
| format | Article |
| id | doaj.art-32bd2dfba979458e9aa7e7f63b11acbc |
| institution | Directory Open Access Journal |
| issn | 1743-422X |
| language | English |
| last_indexed | 2024-03-11T15:15:36Z |
| publishDate | 2023-10-01 |
| publisher | BMC |
| record_format | Article |
| series | Virology Journal |
| spelling | doaj.art-32bd2dfba979458e9aa7e7f63b11acbc2023-10-29T12:14:24ZengBMCVirology Journal1743-422X2023-10-0120111210.1186/s12985-023-02211-yPREB inhibits the replication of prototype foamy virus by affecting its transcriptionJunshi Zhang0Yali Xu1Chenchen Wang2Xiaopeng Tuo3Xingli Zhao4Wentao Qiao5Juan Tan6Key Laboratory of Molecular Microbiology and Technology, Ministry of Education, College of Life Sciences, Nankai UniversityKey Laboratory of Molecular Microbiology and Technology, Ministry of Education, College of Life Sciences, Nankai UniversityKey Laboratory of Molecular Microbiology and Technology, Ministry of Education, College of Life Sciences, Nankai UniversityKey Laboratory of Molecular Microbiology and Technology, Ministry of Education, College of Life Sciences, Nankai UniversityDepartment of Hematology, Oncology Centrer, Tianjin Union Medical CenterKey Laboratory of Molecular Microbiology and Technology, Ministry of Education, College of Life Sciences, Nankai UniversityKey Laboratory of Molecular Microbiology and Technology, Ministry of Education, College of Life Sciences, Nankai UniversityAbstract Background Foamy viruses (FVs) are unique nonpathogenic retroviruses, which remain latent in the host for a long time. Therefore, they may be safe, effective gene transfer vectors. In this study, were assessed FV–host cell interactions and the molecular mechanisms underlying FV latent infection. Methods We used the prototype FV (PFV) to infect HT1080 cells and a PFV indicator cell line (PFVL) to measure virus titers. After 48 h of infection, the culture supernatant (i.e., cell-free PFV particles) and transfected cells (i.e., cell-associated PFV particles) were harvested and incubated with PFVL. After another 48 h, the luciferase activity was used to measure virus titers. Results Through transcriptomics sequencing, we found that PREB mRNA expression was significantly upregulated. Moreover, PREB overexpression reduced PFV replication, whereas endogenous PREB knockdown increased PFV replication. PREB interacted with the Tas DNA-binding and transcriptional activation domains and interfered with its binding to the PFV long terminal repeat and internal promoter, preventing the recruitment of transcription factors and thereby inhibiting the transactivation function of Tas. PREB C-terminal 329–418 aa played a major role in inhibiting PFV replication; PREB also inhibited bovine FV replication. Therefore, PREB has a broad-spectrum inhibitory effect on FV replication. Conclusions Our results demonstrated that PREB inhibits PFV replication by impeding its transcription.https://doi.org/10.1186/s12985-023-02211-yPrototype foamy virusPREBTasTranscription |
| spellingShingle | Junshi Zhang Yali Xu Chenchen Wang Xiaopeng Tuo Xingli Zhao Wentao Qiao Juan Tan PREB inhibits the replication of prototype foamy virus by affecting its transcription Virology Journal Prototype foamy virus PREB Tas Transcription |
| title | PREB inhibits the replication of prototype foamy virus by affecting its transcription |
| title_full | PREB inhibits the replication of prototype foamy virus by affecting its transcription |
| title_fullStr | PREB inhibits the replication of prototype foamy virus by affecting its transcription |
| title_full_unstemmed | PREB inhibits the replication of prototype foamy virus by affecting its transcription |
| title_short | PREB inhibits the replication of prototype foamy virus by affecting its transcription |
| title_sort | preb inhibits the replication of prototype foamy virus by affecting its transcription |
| topic | Prototype foamy virus PREB Tas Transcription |
| url | https://doi.org/10.1186/s12985-023-02211-y |
| work_keys_str_mv | AT junshizhang prebinhibitsthereplicationofprototypefoamyvirusbyaffectingitstranscription AT yalixu prebinhibitsthereplicationofprototypefoamyvirusbyaffectingitstranscription AT chenchenwang prebinhibitsthereplicationofprototypefoamyvirusbyaffectingitstranscription AT xiaopengtuo prebinhibitsthereplicationofprototypefoamyvirusbyaffectingitstranscription AT xinglizhao prebinhibitsthereplicationofprototypefoamyvirusbyaffectingitstranscription AT wentaoqiao prebinhibitsthereplicationofprototypefoamyvirusbyaffectingitstranscription AT juantan prebinhibitsthereplicationofprototypefoamyvirusbyaffectingitstranscription |