Epstein-Barr virus-infected B-chronic lymphocyte leukemia cells express the virally encoded nuclear proteins but they do not enter the cell cycle.

Abstract

Objectives: To understand the mechanism for the refractoriness of B-chronic lymphocyte leukemia (B-CLL) cells for EBV-induced immortalization.

Study design/methods: Cells from four B-CLL patients were infected with Epstein-Barr virus (EBV). Noninfected and infected aliquots were exposed to CD40L. Five days later, the cultures were analyzed for cell survival, activation, DNA synthesis, and expression of EBV-encoded and of cellular regulatory proteins retinoblastoma (Rb), p53, recombinant sequence binding protein (RBP)Jk, and PU.1. The proteins were detected by immunoblotting and by immunofluorescence.

Results: A proportion of the cells were activated and expressed Epstein-Barr nuclear antigens (EBNAs) and elevated Rb level but not latent membrane protein (LMP)-1 and p53. They did not enter the cell cycle. Exposure to CD40L induced DNA synthesis but it did not modify the expression of the EBNAs.

Conclusions: The virus could activate CLL cells, but the full course of the early events that leads to immortalization--as seen in normal B cells--did not proceed beyond a certain point. Compared to B lymphocytes, the critical point is between activation and initiation of the cell cycle.