The Disease Associations of the Antibody Response Against the Epstein-Barr Virus Transactivator Protein ZEBRA Can Be Separated Into Different Epitopes

J Gen Virol. 1995 Jun;76 ( Pt 6):1393-400. doi: 10.1099/0022-1317-76-6-1393.


The BamHI-Z-encoded Epstein-Barr virus (EBV) replication activator (ZEBRA) is a key mediator of the switch from latency to productive cycle in EBV virus. Antibodies against ZEBRA are a marker of EBV reactivation and are regularly found among patients with infectious mononucleosis (IM) or nasopharyngeal carcinoma (NPC), but are only rarely found among healthy EBV-seropositive donors. In order to define the serologically reactive epitopes in the ZEBRA protein, we synthesized a set of overlapping peptides and tested them for reactivity with serum samples from EBV-seronegative persons, patients with NPC, IM, chronic fatigue syndrome, lymphoma or from healthy donors. Three major EBV-specific epitopes were found. These epitopes were further defined and optimized using substitution or truncation analogues of the peptides. Reactivity with epitope number 22 was found in 63% of NPC patients' sera, with < 2% of healthy donors' sera being positive. Serological reactivity with epitope number 19 was associated with IM (57% positive, 5% healthy donors positive). Serum antibodies against epitope 1 were found among healthy donors, but were significantly elevated among patients with NPC, IM or lymphomas. In conclusion, different serologically reactive epitopes in the ZEBRA protein associate with different EBV-associated diseases.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antibodies, Viral / biosynthesis
  • Antibodies, Viral / blood*
  • Antibody Formation*
  • Antibody Specificity
  • DNA-Binding Proteins / immunology*
  • Enzyme-Linked Immunosorbent Assay
  • Epitopes / analysis
  • Epitopes / immunology*
  • Fatigue Syndrome, Chronic / blood
  • Fatigue Syndrome, Chronic / immunology
  • Herpesvirus 4, Human / immunology*
  • Humans
  • Infectious Mononucleosis / blood
  • Infectious Mononucleosis / immunology*
  • Infectious Mononucleosis / virology
  • Lymphoma / blood
  • Lymphoma / immunology
  • Nasopharyngeal Neoplasms / blood
  • Nasopharyngeal Neoplasms / immunology*
  • Nasopharyngeal Neoplasms / virology
  • Peptide Fragments / chemical synthesis
  • Peptide Fragments / immunology
  • Reference Values
  • Trans-Activators / immunology*
  • Viral Proteins / immunology


  • Antibodies, Viral
  • BZLF1 protein, Herpesvirus 4, Human
  • DNA-Binding Proteins
  • Epitopes
  • Peptide Fragments
  • Trans-Activators
  • Viral Proteins