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Blood, Vol. 92 No. 5 (September 1), 1998:
pp. 1721-1727
Antisense to the Epstein-Barr Virus (EBV)-Encoded Latent Membrane
Protein 1 (LMP-1) Suppresses LMP-1 and Bcl-2 Expression and Promotes
Apoptosis in EBV-Immortalized B Cells
Jamie L. Kenney,
Mary E. Guinness,
Tyler Curiel, and
Jill Lacy
From the Department of Internal Medicine, Yale University School of
Medicine, New Haven, CT; and the Department of Internal Medicine,
University of Colorado Health Sciences Center, Denver, CO.
The Epstein-Barr virus (EBV)-encoded latent membrane protein (LMP-1)
is required for viral transformation and functions to protect cells
from apoptotic cell death, in part, by induction of antiapoptotic
genes, including Bcl-2 and A20. We have used antisense
oligodeoxynucleotides targeted to LMP-1 as a strategy to suppress LMP-1
expression and thereby inhibit its functions. We have shown that levels
of LMP-1 protein in EBV-positive lymphoblastoid cell lines can be
reduced by in vitro treatment with unmodified oligodeoxynucleotides
targeted to the first five codons of the LMP-1 open-reading frame.
Furthermore, suppression of LMP-1 was associated with molecular and
phenotypic effects that included downregulation of the LMP-1-inducible
antiapoptotic genes, Bcl-2 and Mcl-1, inhibition of proliferation,
stimulation of apoptosis, and enhancement of sensitivity to the
chemotherapeutic agent, etoposide. These effects were largely
sequence-specific and observed in EBV-positive, but not EBV-negative
cell lines. These studies suggest that lowering expression of LMP-1 in
EBV-associated malignancy might have therapeutic effects and might
synergize with other antitumor agents.
© 1998 by The American Society of Hematology.
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