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Published on: May 15, 2014
PREB inhibits the replication of prototype foamy virus by affecting its transcription
Junshi Zhang1,2, Yali Xu1, Chenchen Wang1
1Key Laboratory of Molecular Microbiology and Technology, Ministry of Education, College of Life Sciences, Nankai University, Tianjin, 300071, China.
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.
Insights
The protein PREB inhibits foamy virus (FV) replication by interfering with viral transcription. This discovery reveals a broad-spectrum antiviral mechanism against FV, including bovine foamy virus.
Area of Science:
- Virology
- Molecular Biology
- Gene Therapy
Background:
- Foamy viruses (FVs) are nonpathogenic retroviruses known for long-term latency in hosts.
- Their latent nature suggests potential as safe and effective gene transfer vectors.
- Understanding FV-host interactions is crucial for vector development.
Purpose of the Study:
- To investigate FV-host cell interactions.
- To elucidate molecular mechanisms behind FV latent infections.
- To identify host factors regulating FV replication.
Main Methods:
- Infection of HT1080 cells and a PFV indicator cell line (PFVL) with prototype foamy virus (PFV).
- Measurement of virus titers using luciferase activity.
- Transcriptomic sequencing to identify host gene expression changes.
Main Results:
- PREB mRNA expression was significantly upregulated post-infection.
- PREB overexpression reduced PFV replication; PREB knockdown increased it.
- PREB directly inhibited the transcriptional transactivation function of the viral Tas protein.
- PREB demonstrated a broad-spectrum inhibitory effect on both PFV and bovine FV replication.
Conclusions:
- PREB inhibits PFV replication by impeding viral transcription.
- PREB acts as a broad-spectrum inhibitor of foamy virus replication.
- This mechanism offers insights into host control of FV infection.
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