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Epstein-Barr Virus Encoded lncRNAs Control the Viral Lytic Switch
Zhixuan Li1,2,3, Yifei Liao1,2,3, Weiyue Ding1
1Division of Infectious Disease, Department of Medicine, Brigham and Women's Hospital, Boston, MA 02115, USA.
Biorxiv : the Preprint Server for Biology
|November 24, 2025
Summary
Epstein-Barr virus (EBV) reactivation is regulated by viral long noncoding RNAs (lncRNAs). A pro-lytic lncRNA triggers reactivation, while a pro-latency lncRNA inhibits it by interacting with CTCF.
Area of Science:
- Virology
- Molecular Biology
- Genetics
Background:
- Epstein-Barr virus (EBV) exhibits a biphasic lifecycle, alternating between latent and lytic phases.
- EBV latency is prevalent in EBV-associated cancers, and reactivation is linked to autoimmune diseases like multiple sclerosis.
- Mechanisms governing EBV reactivation remain incompletely understood.
Purpose of the Study:
- To investigate the regulatory mechanisms controlling the Epstein-Barr virus (EBV) lytic switch.
- To identify novel viral factors involved in EBV reactivation and latency.
Main Methods:
- Multi-omic approaches were employed to analyze EBV lifecycle regulation.
- Investigated the roles of viral long noncoding RNAs (lncRNAs) in EBV reactivation.
- Characterized the interaction of lncRNAs with CTCF and viral genomic elements.
Main Results:
- Identified two counter-regulating viral lncRNAs: one promoting latency and one promoting lytic replication.
- Reactivation triggers rapidly induce the pro-lytic lncRNA, which forms an RNA G-quadruplex interacting with CTCF.
- The pro-lytic lncRNA facilitates the looping of replication enhancers to the lytic promoter, initiating reactivation.
- The pro-latency lncRNA sequesters the pro-lytic lncRNA, preventing CTCF interaction and inhibiting reactivation.
Conclusions:
- Viral lncRNAs are key regulators of the EBV lytic switch.
- The interplay between pro-latency and pro-lytic lncRNAs dictates EBV reactivation.
- These findings provide a foundation for therapeutic strategies targeting EBV reactivation.
Keywords:
CTCFDNA loopingcohesinenhancerepigeneticgamma-herpesvirushistone demethylasehistone methyltransferaselatencylymphomalytic induction therapylytic reactivationpromoterMore Related Videos
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