Function of Lmp2b in Ebv-Positive Burkitt's Lymphoma : Virus and cancer

Bok av Markus Rechsteiner
Epstein-Barr virus (EBV) is a human -herpesvirus that persists latently in the memory B-cell pool. EBV is linked to malignancies including Burkitt's lymphoma (BL) where it expresses specific latency genes. Among these genes, latent membrane protein (LMP)2A and LMP2B seem to be involved in the regulation of EBV latency. LMP2A blocks B-cell receptor (BCR) signalling after its engagement, which activates as well lytic EBV infection. Therefore, LMP2A contributes to the persistence of EBV. By contrast, the function of LMP2B, a splice variant of LMP2A, is still not resolved. The experimental setup presented in this book revealed for the first time that silencing of LMP2B resulted in reduced expression of lytic EBV mRNA and proteins upon BCR cross-linking. By contrast, overexpression of LMP2B resulted in the opposite. We could further demonstrate that LMP2A and LMP2B physically interact and that LMP2B resides predominantly in intracellular compartments. In conclusion, these observations support the hypothesis that LMP2B exhibits a negative regulatory effect on the ability of LMP2A to maintain latent EBV by preventing the switch to lytic infection.