Abstract
Epstein-Barr Virus (EBV) infection is usually benign but immunosuppression can promote post-transplant lymphoproliferative disease (PTLD) and B cell lymphomas in transplant recipients. Latent membrane protein 1 (LMP1) is an important EBV-encoded oncogene that usurps cellular pathways to drive B cell transformation. MicroRNA (miRNA) are tiny, non-coding RNA that regulate cellular gene expression. Since aberrant expression of miRNA has been observed in a variety of malignancies, we hypothesized that modulation of cellular miRNA expression by EBV may play a role in the development of EBV+ B cell lymphomas. Infection of B cell lymphoma lines with EBV significantly modulated expression of miRNA-7, -15b, -221, and -222. Importantly, a similar pattern of microRNA expression was observed in an EBV+ B cell line derived from a patient with PTLD. Activation of a chimeric LMP1 signaling system in EBV negative B lymphoma cell lines also led to induction of miRNA-221 and -222 expression. These mRNA target the cell cycle regulators p27 and p57. Thus, LMP1 can promote cell cycle progression in B cells through miRNA expression. Modulation of miRNA may be a novel mechanism by which EBV drives lymphomagenesis.
