Control of cell cycle entry and apoptosis in B lymphocytes infected by Epstein-Barr virus

Infection of human B cells with Epstein-Barr virus (EBV) results in activat ion of the cell cycle and cell growth. To interpret the mechanisms by which EBV activates the cell,,ve have assayed many proteins involved in control of the G(0) and G(1) phases of the cell cycle and regulation of apoptosis. In EBV infection most of the changes, including the early induction of cycl in D2, are dependent on expression of EBV genes, but an alteration in the E 2F-4 profile was partly independent of viral gene expression, presumably oc curring in response to signal transduction activated when the virus binds t o its receptor, CD21. By comparing the expression of genes controlling apop tosis, including those encoding several members of the BCL-2 family of prot eins, the known relative resistance of EBV-immortalized B cell lines to apo ptosis induced by low serum was found to correlate with expression of both BCL-2 and A20. A20 can be regulated by the NF-kappa B transcription factor, which is known to be activated by the EBV LMP-1 protein. Quantitative assa ys demonstrated a direct temporal relationship between LMP-1 protein levels and active NF-kappa B during the time course of infection.