The labyrinth of interactions of Epstein-Barr virus-encoded small RNAs.

Epstein-Barr Virus (EBV) is an oncogenic herpesvirus implicated in the pathogenesis of a number of human malignancies. However, the mechanism by which EBV leads to malignant transformation is not clear. A number of viral latent gene products, including non-protein coding small RNAs, are believed to be involved. Epstein-Barr virus-encoded RNA 1 (EBER1) and EBER2 are two such RNA molecules that are abundantly expressed (up to 10(7) copies) in all EBV-infected cells, but their function remains poorly understood. These polymerase III transcripts have extensive secondary structure and exist as ribonucleoproteins. An accumulating body of evidence suggests that EBERs play an important role, directly or indirectly, in EBV-induced oncogenesis. Here, we summarize the current understanding of the complex interactions of EBERs with various cellular factors and the potential pathways by which these small RNAs are able to influence EBV-infected cells to proliferate and to induce tumorigenesis. The exosome pathway is probably involved in the cellular excretion of EBERs and facilitating some of their biological effects.