Induction of bcl-2 Expression by Epstein-Barr Virus Latent Membrane Protein 1 Protects Infected B Cells From Programmed Cell Death

Cell. 1991 Jun 28;65(7):1107-15. doi: 10.1016/0092-8674(91)90007-l.

Abstract

Epstein-Barr virus (EBV) not only induces growth transformation in human B lymphocytes, but has more recently been shown to enhance B cell survival under suboptimal conditions where growth is inhibited; both effects are mediated through the coordinate action of eight virus-coded latent proteins. The effect upon cell survival is best recognized in EBV-positive Burkitt's lymphoma cell lines where activation of full virus latent gene expression protects the cells from programmed cell death (apoptosis). Here we show by DNA transfection into human B cells that protection from apoptosis is conferred through expression of a single EBV latent protein, the latent membrane protein LMP 1. Furthermore, we demonstrate that LMP 1 mediates this effect by up-regulating expression of the cellular oncogene bcl-2. The interplay between EBV infection and expression of this cellular oncogene has important implications for virus persistence and for the pathogenesis of virus-associated malignant disease.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antigens, Viral / physiology*
  • B-Lymphocytes / cytology*
  • Cell Line
  • Cell Survival*
  • DNA Damage
  • Gene Expression Regulation
  • Gene Expression Regulation, Viral
  • Herpesvirus 4, Human / physiology*
  • Humans
  • In Vitro Techniques
  • Proto-Oncogene Proteins / physiology*
  • Proto-Oncogene Proteins c-bcl-2
  • Transfection
  • Viral Matrix Proteins*

Substances

  • Antigens, Viral
  • EBV-associated membrane antigen, Epstein-Barr virus
  • Proto-Oncogene Proteins
  • Proto-Oncogene Proteins c-bcl-2
  • Viral Matrix Proteins