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Updated: Sep 16, 2025

08:51
Genome-wide RNAi Screening to Identify Host Factors That Modulate Oncolytic Virus Therapy
Published on: April 3, 2018
9.2K
Oncogenic virus hijacks SOX18 pioneer function to enhance viral persistence
Biorxiv : the Preprint Server for Biology
|July 9, 2025
Summary
Kaposi
Area of Science:
- Virology
- Molecular Biology
- Oncology
Background:
- Kaposi's sarcoma herpesvirus (KSHV) establishes lifelong infections, often in lymphatic endothelial cells (LECs).
- Viral episomal genome maintenance is crucial for persistent KSHV infection but its regulation is not fully understood.
- The viral protein LANA is essential for KSHV episome stability.
Purpose of the Study:
- To investigate the cell-type-specific mechanisms KSHV employs for episomal genome maintenance.
- To identify host factors that contribute to KSHV episome persistence in lymphatic endothelial cells.
Main Methods:
- Investigated the role of the endothelial-specific transcription factor SOX18 in KSHV infection.
- Utilized genetic and pharmacological disruption of SOX18 and the SWI/SNF complex subunit BRG1.
- Assessed viral episome load and hallmarks of KSHV infection.
Main Results:
- KSHV hijacks the pioneering function of SOX18 in LECs to maintain viral episomes.
- LANA recruits the SWI/SNF complex subunit BRG1 through SOX18, enhancing chromatin accessibility for viral genome persistence.
- Disruption of SOX18 or BRG1 significantly reduces viral episome load and infection hallmarks.
Conclusions:
- KSHV exploits the endothelial-specific transcription factor SOX18 for efficient episomal genome maintenance.
- This interaction facilitates viral persistence by recruiting chromatin-remodeling complexes.
- Targeting this pathway offers potential strategies to control KSHV infections.
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