In summary, our results here reveal that activation of the IRF6 transcription factor is critical for lytic EBV reactivation and cellular differentiation in EBV-infected NOKs and suggest that the ability of latent EBV infection to inhibit IRF6 expression in epithelial cells is an important mechanism by which EBV promotes the early development of undifferentiated NPC and GC in humans. The gene discussed is IRF6; the disease is gastric cancer.