Division of Tumor Virology, Dana-Farber Cancer Institute, Boston, Massachusetts.
J Virol 64: 1227-32 (1990)
Abstract
Expression of the Epstein-Barr virus (EBV) BZLF1 gene in latently
infected lymphocytes is sufficient to trigger the viral lytic cycle. As
shown in the accompanying report (E. Flemington and S.H. Speck, J.
Virol. 64:1217-1226, 1990), the promoter for the BZLF1 gene (Zp)
contains two distinct types of elements (ZI and ZII [an AP-1-like
domain]) which are responsive to the phorbol ester
12-O-tetradecanoylphorbol-13-acetate (TPA), an inducer of the viral
lytic cycle. Although Zp can be activated with TPA in an EBV-negative
Burkitt's lymphoma cell line (Ramos), its activity is considerably lower
than in EBV-positive cell lines which can be induced with TPA. Here we
show that the protein product of the BZLF1 gene (ZEBRA) can
transactivate its own promoter by a mechanism which involves direct
binding to a region distinct from the ZI and ZII element. Moreover, we
show that this region is composed of two distinct
ZEBRA-binding-transactivation domains. Interestingly, these two domains
are not homologous, and while one domain (ZIIIA) is similar to
previously described ZEBRA-binding domains, the second (ZIIIB) is a
higher-affinity site which bears no detectable homology to the consensus
ZEBRA recognition sequence. We also show that transactivation is
independent of the otherwise essential ZII domain, suggesting that ZEBRA
binding may functionally replace or supercede the need for a functional
ZII domain. This observation supports a model for activation of the
lytic cycle whereby synthesis of a critical level of ZEBRA signals
commitment to BZLF1 transcription and initiation of the lytic cascade.
Mesh Headings
Unique Identifier: 90156520
Chemical Identifiers (Names)