Effects of Epstein-Barr Virus Latent Membrane Protein 2A (LMP2A) on cytokine production in primary and transformed B cells (105.40)

Abstract

Abstract Epstein-Barr Virus (EBV) latently-infected B cells are precursors of EBV-associated malignancies. However, the transition from a latently-infected cell to a malignant tumor cell is poorly understood. Studies show that EBV modulates pro-survival and anti-inflammatory cytokine levels in EBV-transformed cell lines. However, gene expression in these cell lines may not reflect gene expression found in latent B cells and lymphomas. One EBV protein, LMP2A, is consistently detected in both latently-infected resting B cells, as well as in EBV-associated malignancies. Therefore, we hypothesized that LMP2A may modulate cytokines that aid in the transition between latency and malignancy. Cytokine array data analyzing B cells from LMP2A-transgenic mice and B cell lymphomas expressing LMP2A indicate that LMP2A does not globally alter B cell-produced cytokine levels, but rather targets a limited number of cytokines. Additional studies using ELISA and Real-time RT-PCR confirm that LMP2A increases IL-10 levels and flow cytometry reveals that LMP2A increases the amount of IL-10 produced per B cell. Inhibitors of the LMP2A signaling pathway are being tested to determine the signaling requirements for LMP2A-mediated increases in IL-10. These data identify a novel function of LMP2A in the alteration of a cytokine that is important for both tumor survival and anti-tumor responses.