Epstein-Barr Virus-Infected B-chronic Lymphocyte Leukemia Cells Express the Virally Encoded Nuclear Proteins but They Do Not Enter the Cell Cycle

J Hum Virol. May-Jun 2000;3(3):125-36.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • B-Lymphocytes / metabolism
  • B-Lymphocytes / virology*
  • Blotting, Western
  • Cell Cycle
  • DNA-Binding Proteins / analysis
  • Epstein-Barr Virus Nuclear Antigens / analysis
  • Flow Cytometry
  • Herpesvirus 4, Human*
  • Humans
  • Immunoglobulin J Recombination Signal Sequence-Binding Protein
  • Immunohistochemistry
  • Ki-67 Antigen / analysis
  • Leukemia, Lymphocytic, Chronic, B-Cell / immunology*
  • Lymphocyte Activation
  • Nuclear Proteins*
  • Tumor Cells, Cultured
  • Tumor Suppressor Protein p53 / analysis
  • Viral Matrix Proteins / analysis

Substances

  • DNA-Binding Proteins
  • EBV-associated membrane antigen, Epstein-Barr virus
  • Epstein-Barr Virus Nuclear Antigens
  • Immunoglobulin J Recombination Signal Sequence-Binding Protein
  • Ki-67 Antigen
  • Nuclear Proteins
  • RBPJ protein, human
  • Tumor Suppressor Protein p53
  • Viral Matrix Proteins