Division of Tumor Virology, Dana-Farber Cancer Institute, Boston, Massachusetts 02115, USA.
Virology 209: 225-9 (1995)
Abstract
The Epstein-Barr virus (EBV) BZLF1 gene is expressed early upon
induction of the viral lytic cycle and its protein product is unique in
its ability to disrupt viral latency in some latently infected cell
lines. Anti-immunoglobulin (anti-Ig) treatment of the Burkitt's lymphoma
cell line Akata, which bears surface IgG, has previously been shown to
synchronously induce transcription of the BZLF1 gene (K. Takada and Y.
Ono, 1989, J. Virol. 63, 445-449). We have previously shown that anti-Ig
induction of Akata cells activates expression of the tumor necrosis
factor alpha (TNF-alpha) gene via a calcineurin-dependent mechanism
(Goldfeld et al., 1992, Proc. Natl. Acad. Sci. USA 89, 12198-12201).
Here, we report that anti-Ig induction of the EBV lytic cycle in Akata
cells can be blocked by the immunosuppressants cyclosporin A and FK506.
Furthermore, we demonstrate that synergistic induction by phorbol ester
and calcium ionophore of a BZLF1 promoter-driven reporter construct in
an EBV-negative BL cell line can be inhibited by addition of cyclosporin
A. Thus, analogous to activation of TNF-alpha gene in Akata cells,
anti-Ig induction of the BZLF1 promoter is most likely mediated by
calcineurin and probably involves translocation to the nucleus of a
transcription factor sequestered in the cytoplasm. As such,
immunosuppressants may be useful probes for dissecting B cell activation
pathways involved in regulating EBV gene transcription.
Mesh Headings
Unique Identifier: 95266311
Gene Symbols
Chemical Identifiers (Names)