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Blood, Vol. 93 No. 9 (May 1), 1999:
pp. 3026-3032
Expression of Epstein-Barr Virus BamHI-A Rightward Transcripts
in Latently Infected B Cells From Peripheral Blood
Honglin Chen,
Paul Smith,
Richard F. Ambinder, and
S. Diane Hayward
From the Molecular Virology Laboratory, the Department of
Pharmacology and Molecular Science, and the Department of Oncology,
Johns Hopkins School of Medicine, Baltimore, MD; and the Ludwig
Institute for Cancer Research, Imperial College School of Medicine at
St Mary's, London, UK.
In addition to the Epstein-Barr virus (EBV) EBNA and LMP latency
genes, there is a family of alternatively spliced BamHI-A rightward transcripts (BARTs). These latency transcripts are highly expressed in the EBV-associated malignancies nasopharyngeal carcinoma and Burkitt's lymphoma, and are expressed at lower levels in latently EBV-infected B-cell lines. The contribution of the BARTs to EBV biology
or pathogenesis is unknown. Resting B cells have recently been
recognized as a reservoir for EBV persistence in the peripheral blood.
In these cells, EBV gene expression is tightly restricted and the only
viral gene known to be consistently expressed is LMP2A. We used cell
sorting and reverse-transcriptase polymerase chain reaction (RT-PCR) to
examine whether BARTs are expressed in the restricted form of in vivo
latency. Our results demonstrated that RNAs with splicing diagnostic
for transcripts containing the BART RPMS1 and BARFO open-reading frames
(ORFs) were expressed in CD19+ but not in
CD23+ B cells isolated from peripheral blood of healthy
individuals. The product of the proximal RPMS1 ORF has not previously
been characterized. The RPMS1 ORF was shown to encode a 15-kD protein that localized to the nucleus of transfected cells. Expression of the
BARTs in peripheral blood B cells suggests that the proteins encoded by
these transcripts are likely to be important for maintenance of in vivo latency.
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