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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.