Therapeutic Approaches to Targetting Epstein-Barr Virus Related Disease

Epstein-Barr virus infection is associated with several lymphoid and epithelial malignancies. The replication and persistence of the EBV genome in latently infected cells is dependent on the homodimer formation of EBV nuclear antigen 1 (EBNA1) and it’s binding to the cognate EBV OriP element. Current chemotherapeutic treatments of EBV-positive malignancies are non-specific to the EBV status of the disease. We have designed and synthesised eight small peptides using Solid Phase Peptide Synthesis, aimed to prevent EBNA1 homodimer formation and destabilise existing homodimers. These putative dimer inhibitory peptides (DIP), designed to mimic the proline loop of the protein (which stabilises the dimer) are attached to the cell penetrating peptide TAT, to act as competitive inhibitors in the nucleus of infected cells. Data will be presented on the effect of these peptides on multiple EBV dependent and independent tumour B cell lines, with respect to cell penetration, cell viability and protein dimerisation. These peptides may provide a novel approach to treating EBV positive and dependent disease by inhibiting viral persistence, and possibly the cell survival properties of EBNA1