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The disease associations of the antibody response against the EB virus transactivator protein ZEBRA can be separated into different epitopes

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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.

Tedeschi R, Foong YT, Cheng HM, dePaoli P, Lehtinen T, Elfborg T,
Dillner J

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