Epstein-Barr viral nuclear antigen 1 antisense oligodeoxynucleotide
inhibits proliferation of Epstein-Barr virus-immortalized B cells
G Roth, T Curiel and J Lacy
University of Colorado Health Sciences Center, Denver.
The Epstein-Barr virus (EBV) nuclear antigen 1 (EBNA-1) is a latent viral
protein that is expressed in all EBV-immortalized lymphocytes and plays an
essential role in immortalization y EBV. EBNA-1 protein is required for
replication and maintenance of the episomal viral genome in latently
infected, immortalized cells. Given the essential function of EBNA-1 in
immortalization, we have examined the effect of EBNA-1 antisense
oligodeoxynucleotides on expression of EBNA-1 protein and proliferation in
EBV-immortalized lymphoblastoid cells. We have shown that exposure to
unmodified antisense oligodeoxynucleotide of codons 6 through 10 of EBNA-1
partially suppressed EBNA-1 protein expression in EBV-immortalized
lymphoblastoid cells relative to untreated cells or cells exposed to two
scrambled sequences of the EBNA-1 antisense. Furthermore, EBNA-1 antisense
inhibited proliferation of EBV- immortalized cells by at least 50% compared
with the scrambled antisense sequences. There was no difference in the
effect of antisense and scrambled antisense oligodeoxynucleotides on the
proliferation of EBV-negative cells, indicating that the antiproliferative
effect of EBNA-1 antisense was EBV-specific. These findings underscore the
essential role of EBNA-1 in immortalization and, furthermore, have
potential therapeutic implications for EBV-associated neoplastic diseases.
Volume 84,
Issue 2,
pp. 582-587,
07/15/1994
Copyright © 1994 by The American Society of Hematology
