Quantitative analysis of Epstein-Barr virus (EBV)-related gene expression in patients with chronic active EBV infection

Chronic active EBV (CAEBV) infection is a persistent lymphoproliferative disorder with unclear pathogenesis and no standard treatment. This study quantified EBV gene expression in peripheral blood samples from 24 CAEBV patients using real-time RT-PCR, measuring six latent genes (EBNA1, EBNA2, LMP1, LMP2, EBER1, BARTs) and two lytic genes (BZLF1, gp350/220). Results showed a latency type II pattern: EBER1 and BARTs were abundantly expressed in all patients, LMP2 in most patients, while EBNA1 and LMP1 were detected less frequently and at lower levels. EBNA2 and lytic genes were not detected in any patient. Notably, EBNA1 expression was significantly higher and more frequent in clinically active patients (severe symptoms) compared to inactive patients. The correlation between gene expression and viral DNA load was significant for all genes examined. Cell sorting revealed that expression profiles matched primarily infected cell populations. Gene expression patterns did not predict disease outcome. The authors conclude that quantifying EBV gene expression may help clarify CAEBV pathogenesis and guide immunotherapeutic approaches targeting LMP2 as the most favorable CTL therapy target.

Key findings

• CAEBV shows latency type II EBV gene expression with abundant EBER1 and BARTs, moderate LMP2, and reduced EBNA1 and LMP1 expression; lytic genes were undetected in all patients
• EBNA1 expression levels were 8.3 times higher in clinically active patients compared to inactive patients, suggesting a role in symptom pathogenesis
• All eight EBV genes examined showed significant correlation with EBV DNA load in peripheral blood
• LMP2 is identified as the most favorable target for EBV-specific cytotoxic T lymphocyte (CTL) immunotherapy in CAEBV due to abundant expression of non-translatable EBER1 and BARTs