Transient expression of the Epstein-Barr virus LMP1 gene in human primary B cells induces cellular activation and DNA synthesis

Oncogene. 1992 Sep;7(9):1775-82.


The Epstein-Barr virus (EBV)-encoded latent membrane protein 1 (LMP1) and Epstein-Barr virus nuclear antigen 2 (EBNA2) are expressed in EBV-immortalized human B cells. It has previously been shown that transfection of the LMP1 and EBNA2 genes into Burkitt's lymphoma cell lines results in the up-regulation of CD23, CD21, ICAM-1 and LFA-1 cell-surface proteins. In the present study, the effects of transient expression of the LMP1 and EBNA2 genes were studied in normal primary human B cells pretreated with UV-inactivated EBV particles. To identify and purify cells which express the transfected DNA we used a gene encoding a surface molecule, CD2, as a co-transfection marker. We show that transient expression of the LMP1 gene, from heterologous promoters, is sufficient to induce cellular enlargement and up-regulation of surface expression of the activation markers CD23, CD21, ICAM-1 and LFA-1 in primary B cells. Most importantly, we show that transient expression of the LMP1 gene is sufficient to induce DNA synthesis in human primary B cells. Transient EBNA2 expression enhanced the effect of transient LMP1 expression on CD21 and CD23 cell-surface expression but, under our experimental conditions, inhibited the induction of DNA synthesis by LMP1. We conclude that activation of primary B cells with inactivated EBV particles, followed by transient expression of only two viral genes, EBNA2 and LMP1, is sufficient to reconstitute some of the early events of B-cell immortalization by EBV.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antigens, Differentiation, T-Lymphocyte / analysis
  • Antigens, Viral / analysis
  • Antigens, Viral / genetics*
  • Antigens, Viral / toxicity
  • B-Lymphocytes / microbiology*
  • CD2 Antigens
  • DNA / biosynthesis*
  • Epstein-Barr Virus Nuclear Antigens
  • Gene Expression*
  • Genes, Viral*
  • Herpesvirus 4, Human / genetics*
  • Humans
  • Lymphocyte Activation*
  • Phorbol 12,13-Dibutyrate / pharmacology
  • Receptors, Immunologic / analysis
  • Transcription, Genetic
  • Up-Regulation
  • Viral Matrix Proteins*


  • Antigens, Differentiation, T-Lymphocyte
  • Antigens, Viral
  • CD2 Antigens
  • EBV-associated membrane antigen, Epstein-Barr virus
  • Epstein-Barr Virus Nuclear Antigens
  • Receptors, Immunologic
  • Viral Matrix Proteins
  • Phorbol 12,13-Dibutyrate
  • DNA