Epstein-Barr Virus Latent Membrane Protein 2A protects B cells from MYC-induced apoptosis and accelerates tumor development (45.14)

Abstract

Abstract Despite its initial isolation from Burkitt's lymphoma (BL) tumors over 40 years ago, the exact contribution of Epstein-Barr Virus (EBV) to BL is undefined. EBV encodes for multiple proteins in latently-infected B cells that affect B cell survival and activation. Due to the ability of one of these latency proteins, latent membrane protein 2A (LMP2A) to protect B cells from apoptosis, we tested if LMP2A protects B cells from apoptosis induced by aberrant c-MYC expression that precedes and dominates BL. We crossed LMP2A-transgenic mice (LMP2A-Tg) in which all B cells express LMP2A to a transgenic mouse that expresses a BL translocation of myc (λ-MYC-Tg mice). LMP2A protects B cells from MYC-induced apoptosis and accelerates the development of B cell lymphomas in LMP2A/λ-MYC-Tg mice. LMP2A also increases the expression of Bcl-XL in both pre-tumor B cells and tumor cells, suggesting a mechanism for LMP2A mediated B cell survival in the presence of MYC. These results support a hypothesis that EBV LMP2A promotes tumor development by protecting pre-tumor B cells that would normally apoptose after the c-myc translocation. This work is supported by Public Health Service grants CA62234 and CA73507 from the NCI.