A role for the protease MALT1 in EBV-mediated B-cell transformation by Latent Membrane Proteins 1 and 2

Latency proteins of the virus contribute to lymphomagenesis by activating the transcription factor NF-kB, but the molecular mechanism underlying EBV-driven NF-kB activation remains incompletely understood. Here we show that EBV latent membrane proteins LMP1 and LMP2A or LMP2B synergize to activate the protease MALT1, a key driver of NF-kB-mediated lymphocyte proliferation.

EBV-positive B-cell lines co-expressing LMP1 and LMP2 proteins exhibited constitutive activity of the protease MALT1, and treatment with a MALT1 inhibitor or silencing of latent membrane protein-1 (LMP1) or LMP2 impaired MALT1-dependent substrate cleavage and proliferation in these cell lines. Further molecular studies revealed that LMP1 physically interacted with the MALT1-binding partner BCL10, while LMP2A and LMP2B interacted with MALT1.