Fig. 8.

EBNA1 alters the cellular oxidative balance to promote cell immortalization and oncogenesis. EBNA1 is the only viral protein regularly expressed in all types of EBV carrying normal and malignant cells. The expression of EBNA1 is associated with a shift of the cellular redox status that correlates with transcriptional activation of the catalytic subunit of the NADPH oxidase NOX2. High levels of ROS are required for efficient expression of cellular and viral genes that sustain B-cell proliferation and immortalization, including the viral latent membrane protein LPM1. While inducing the establishment of an oxidative environment that promotes infection, EBNA1 limits the antiproliferative response triggered by oxidated DNA via activation of both the nucleotide sanitization pathway that prevents the incorporation of oxidated nucleotides, and repair pathways that purge DNA from oxidized bases. The persistent oxidative stress induced by EBNA1 is associated with genomic instability, which promotes carcinogenesis and renders EBV infected cells particularly sensitive to disturbance of the redox balance by the inhibition of antioxidant pathways