EBNA2 is required for protection of latently Epstein-Barr virus-infected B cells against specific apoptotic stimuli

J Virol. 2004 Nov;78(22):12694-7. doi: 10.1128/JVI.78.22.12694-12697.2004.

Abstract

In addition to functioning as a transcriptional transactivator, Epstein-Barr virus EBNA2 interacts with Nur77 to protect against Nur77-mediated apoptosis. Estrogen-regulated EBNA2 in EREB2-5 cells was replaced by either EBNA2 or EBNA2 with a deletion of conserved region 4 (EBNA2DeltaCR4). Both EBNA2-converted and EBNA2DeltaCR4-converted EREB2-5 cells grew in the absence of estrogen and expressed LMP1. Treatment with tumor necrosis factor alpha did not induce apoptosis of EBNA2- or EBNA2DeltaCR4-expressing cells, but EBNA2DeltaCR4 cells were susceptible to etoposide and 5-fluorouracil, Nur77-mediated inducers of apoptosis. Thus, EBNA2 protects B cells against specific apoptotic agents against which LMP1 is not effective.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Apoptosis*
  • B-Lymphocytes / cytology
  • B-Lymphocytes / virology*
  • DNA-Binding Proteins / physiology
  • Epstein-Barr Virus Nuclear Antigens / physiology*
  • Herpesvirus 4, Human / physiology*
  • Nuclear Receptor Subfamily 4, Group A, Member 1
  • Receptors, Cytoplasmic and Nuclear
  • Receptors, Steroid
  • Transcription Factors / physiology
  • Tumor Necrosis Factor-alpha / pharmacology
  • Viral Matrix Proteins / physiology
  • Viral Proteins
  • Virus Latency

Substances

  • DNA-Binding Proteins
  • EBNA-2 protein, Human herpesvirus 4
  • EBV-associated membrane antigen, Epstein-Barr virus
  • Epstein-Barr Virus Nuclear Antigens
  • NR4A1 protein, human
  • Nuclear Receptor Subfamily 4, Group A, Member 1
  • Receptors, Cytoplasmic and Nuclear
  • Receptors, Steroid
  • Transcription Factors
  • Tumor Necrosis Factor-alpha
  • Viral Matrix Proteins
  • Viral Proteins