Comparative proteomic analysis implicates COMMD proteins as Epstein-Barr virus targets in the BL41 Burkitt's lymphoma...

Epstein-Barr virus (EBV) infection is a major health problem associated with a variety of diseases, including Burkitt's lymphoma. EBV promotes its effects through the activation of multiple signaling pathways, with NF-κB mediated transcription being a major target. We have undertaken a comparative proteomic approach using 2D-electrophoresis and mass spectrometry to identify EBV-regulated proteins in the BL41 Burkitt's lymphoma cell line. Many of the proteins differentially regulated were previously known mediators of EBV action. Among the novel proteins identified, three members of the conserved COMMD family were found to be down-regulated. Further analysis of this family at the mRNA level, using reverse-transcriptase or real-time PCR, showed that 7 out of 10 COMMD members were affected in EBV-transformed BL41 cells. Since COMMD family proteins have been implicated as negative regulators of the NF-κB transcription factor, our data are consistent with a hypothesis that EBV down-regulates COMMD proteins in order to enhance NF-κB mediated transcriptional events and B-lymphocyte transformation.