title: The disease associations of the antibody response against the Epstein-Barr virus transactivator protein ZEBRA can be separated into different epitopes.
abstract: 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.
authors.affiliation: Microbiology and Tumor Biology Center, Karolinska Institute, Stockholm, Sweden.
authors.forename: R
authors.initials: R
authors.lastname: Tedeschi
authors.forename: Y T
authors.initials: YT
authors.lastname: Foong
authors.forename: H M
authors.initials: HM
authors.lastname: Cheng
authors.forename: P
authors.initials: P
authors.lastname: dePaoli
authors.forename: T
authors.initials: T
authors.lastname: Lehtinen
authors.forename: T
authors.initials: T
authors.lastname: Elfborg
authors.forename: J
authors.initials: J
authors.lastname: Dillner
mesh_terms: D000914:Antibodies, Viral / Q000096:biosynthesis / Q000097:blood*; D000917:Antibody Formation; D000918:Antibody Specificity; D004268:DNA-Binding Proteins / Q000276:immunology*; D004797:Enzyme-Linked Immunosorbent Assay; D000939:Epitopes / Q000032:analysis / Q000276:immunology*; D015673:Fatigue Syndrome, Chronic / Q000097:blood / Q000276:immunology; D004854:Herpesvirus 4, Human / Q000276:immunology*; D006801:Humans; D007244:Infectious Mononucleosis / Q000097:blood / Q000276:immunology* / Q000821:virology; D008223:Lymphoma / Q000097:blood / Q000276:immunology; D009303:Nasopharyngeal Neoplasms / Q000097:blood / Q000276:immunology* / Q000821:virology; D010446:Peptide Fragments / Q000138:chemical synthesis / Q000276:immunology; D012016:Reference Values; D015534:Trans-Activators / Q000276:immunology*; D014764:Viral Proteins / Q000276:immunology
chemical_list: D000914:Antibodies, Viral; C063676:BZLF1 protein, Herpesvirus 4, Human; D004268:DNA-Binding Proteins; D000939:Epitopes; D010446:Peptide Fragments; D015534:Trans-Activators; D014764:Viral Proteins