B Cell Receptor-Responsive miR-141 Enhances Epstein-Barr Virus Lytic Cycle via FOXO3 Inhibition.

Area of Science:

• Virology
• Molecular Biology
• Immunology

Background:

• Epstein-Barr virus (EBV) reactivation is triggered by B cell receptor (BCR) signaling.
• Host microRNAs (miRNAs) can influence EBV's lytic cycle, but their roles are not fully understood.
• Previous work identified EBV miRNAs that dampen BCR signaling and lytic reactivation.

Purpose of the Study:

• To investigate the role of host and viral miRNAs in EBV lytic replication following BCR-mediated reactivation.
• To identify molecular targets common to host miR-141 and viral miR-BART9.
• To elucidate the function of these miRNAs and their targets in the EBV lytic cascade.

Main Methods:

• Small RNA profiling in reactivated Burkitt lymphoma cells.
• Bioinformatic analysis and experimental validation of miRNA targets.
• Functional assays to assess the impact of miRNAs and targets on EBV lytic progression.

Main Results:

• miR-141 was identified as a host miRNA induced by BCR cross-linking.
• EBV encodes miR-BART9, which shares sequence homology with miR-141.
• Both miRNAs target B cell transcription factors and EBV immediate-early gene regulators, including FOXO3.
• miR-141, miR-BART9, and FOXO3 play roles in modulating the kinetics of the EBV lytic cycle.

Conclusions:

• EBV exploits BCR-responsive host miR-141 and mimics its activity with viral miR-BART9 to enhance lytic replication.
• FOXO3 is a key target suppressed by both host and viral miRNAs, regulating EBV lytic cycle progression.
• This study reveals a mechanism by which EBV utilizes miRNAs to support its lytic phase after reactivation triggers.