EBNA2 and activated Notch induce expression of BATF

Area of Science:

• Virology
• Molecular Biology
• Immunology

Background:

• Epstein-Barr virus (EBV) infection immortalizes human B lymphocytes.
• This process requires the viral transactivator EBNA2 and cellular gene products.
• EBNA2 targets viral and cellular genes to achieve B cell immortalization.

Purpose of the Study:

• To identify cellular genes regulated by EBNA2 during EBV infection.
• To investigate the function of the identified gene in B cell immortalization and EBV latency.
• To understand the coordination of viral and cellular gene expression in EBV pathogenesis.

Main Methods:

• Infection of human B cells (established and primary) with EBV.
• Analysis of BATF gene expression levels post-infection.
• Investigating BATF transactivation by EBNA2 and Notch signaling.
• Assessing BATF's role in regulating BZLF1 reporter gene expression and lytic replication.

Main Results:

• BATF was identified as a cellular gene dramatically upregulated within 24 hours of EBV infection.
• EBNA2 mediates BATF transactivation in a B-cell-specific manner, mimicked by Notch signaling.
• BATF encodes a transcription factor that negatively regulates AP-1 activity and antagonizes cell growth.
• BATF negatively impacted BZLF1 reporter gene expression and reduced EBV lytic replication.

Conclusions:

• BATF is a novel cellular target of EBV-encoded EBNA2 in human B cells.
• BATF functions as a negative regulator of AP-1 and cell growth, potentially promoting EBV latency.
• The identification of BATF provides insights into the coordinated regulation of viral and cellular genes for EBV latency and replication control.