Inhibition of antigen processing by the internal repeat region of the Epstein-Barr virus nuclear antigen-1

Nature. 1995 Jun 22;375(6533):685-8. doi: 10.1038/375685a0.


The Epstein-Barr virus (EBV)-encoded nuclear antigen (EBNA1) is expressed in latently EBV-infected B lymphocytes that persist for life in healthy virus carriers, and is the only viral protein regularly detected in all malignancies associated with EBV. Major histocompatibility complex (MHC) class I-restricted, EBNA1-specific cytotoxic T lymphocyte (CTL) responses have not been demonstrated. Using recombinant vaccinia viruses encoding chimaeric proteins containing an immunodominant human leukocyte antigen A11-restricted CTL epitope, amino acids 416-424 of the EBNA4 protein, inserted within the intact EBNA1, or within an EBNA1 deletion mutant devoid of the internal Gly-Ala repetitive sequence, we demonstrate that the Gly-Ala repeats generate a cis-acting inhibitory signal that interferes with antigen processing and MHC class I-restricted presentation. Insertion of the Gly-Ala repeats downstream of the 416-424 epitope inhibited CTL recognition of a chimaeric EBNA4 protein. The results highlight a previously unknown mechanism of viral escape from CTL surveillance, and support the view that the resistance of cells expressing EBNA1 to rejection mediated by CTL is a critical requirement for EBV persistence and pathogenesis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antigen Presentation*
  • Antigens, Viral / genetics
  • Antigens, Viral / immunology*
  • Base Sequence
  • Cell Line
  • DNA-Binding Proteins / genetics
  • DNA-Binding Proteins / immunology*
  • Epitopes / genetics
  • Epitopes / immunology
  • Epstein-Barr Virus Nuclear Antigens
  • Fibroblasts
  • HLA-A Antigens / immunology
  • HLA-A11 Antigen
  • Herpesvirus 4, Human / immunology*
  • Humans
  • Molecular Sequence Data
  • Oligodeoxyribonucleotides
  • Recombinant Fusion Proteins / genetics
  • Recombinant Fusion Proteins / immunology
  • T-Lymphocytes, Cytotoxic / immunology*
  • Vaccinia virus / genetics


  • Antigens, Viral
  • DNA-Binding Proteins
  • Epitopes
  • Epstein-Barr Virus Nuclear Antigens
  • HLA-A Antigens
  • HLA-A11 Antigen
  • Oligodeoxyribonucleotides
  • Recombinant Fusion Proteins