Epstein-barr virus genome replication as a molecular target for cancer therapy

Epstein-Barr virus (EBV), a human oncogenic virus, is a B cell-tropic herpesvirus and has the ability to immortalize normal B cells during latent infection. The Epstein-Barr nuclear antigen 1 (EBNA1) protein of EBV is expressed in the most EBV latently infected cells and binds to a specific viral genome region termed “oriP” (origin of plasmid replication) to maintain the stability of the approximately 170 kb double-stranded circular virus genomic DNA (episome) in cells. EBV elimination is thought to inhibit progression of EBV-associated malignancies, and the EBNA1-dependent mechanisms for EBV episome replication and maintenance are considered to be novel molecular targets for anti-EBV therapy. We have explored small-molecule compounds that can inhibit the binding between EBNA1 protein and oriP and found one pyrrole imidazole polyamide named DSE3 which can also inhibit EBV-mediated immortalization of normal B cells. These data suggested that an EBNA1-targeting strategy could be useful to combat EBV-associated malignancies.