New Insights Into How Epstein-Barr Virus Protein EBNA-LP Alters DNA to Cause Cancer

Scientists at The Wistar Institute have uncovered a crucial mechanism by which the Epstein-Barr virus (EBV), a widespread pathogen infecting over 90% of the global population, influences cellular DNA to promote cancer development. The study focuses on the viral protein EBNA-LP, revealing that it actively rewires the three-dimensional organization of host DNA within infected B cells. This process facilitates the unlocking of previously restricted genome regions, enabling abnormal gene activation that promotes oncogenic transformation.

Published in Nucleic Acids Research, the research shows that EBNA-LP interacts with YY1, a host protein responsible for maintaining DNA architecture. Using advanced mapping techniques like HiChIP, the team demonstrated that EBNA-LP disrupts normal DNA folding, effectively opening locked genomic 'doors' and allowing the transcription of genes that are usually inactive. This genome reprogramming shifts B cells into a more naive, stem-cell-like state, increasing their plasticity and susceptibility to malignant transformation.

Traditionally considered a helper protein, EBNA-LP is now shown to have a distinct and pivotal role in viral-induced carcinogenesis. The study also indicates that EBNA-LP works alongside other viral proteins, EBNA1 and EBNA2, targeting the same cellular processes to manipulate DNA structure. This multifaceted approach underscores how EBV utilizes multiple tools to ensure persistent infection and tumor formation.

Understanding how EBNA-LP reprograms host genomes provides valuable insight into viral oncogenesis and highlights potential therapeutic targets. Currently, treatments for EBV-related diseases mainly address symptoms, but this research opens avenues for developing strategies that directly target viral mechanisms. Furthermore, the findings suggest similar genome remodeling processes may underlie other types of cancer caused by genetic mutations, offering broader implications for cancer therapy.

By studying viral manipulation techniques, researchers gain a window into fundamental cellular processes. As Tempera emphasizes, viruses like EBV exploit existing cellular tools, and unraveling these interactions can lead to innovative approaches to treat or prevent virus-associated cancers.