Division of Tumor Virology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, Massachusetts 02115, USA.
J Virol 69: 4206-12 (1995)
Abstract
The lytic switch transactivator Zta initiates the ordered cascade of
Epstein-Barr virus gene expression that culminates in virus production.
Zta is a sequence-specific DNA-binding protein that transactivates early
viral promotes via cis-acting sequences. Activation of some of these
genes is mediated through binding to consensus AP-1 promoter elements.
This observation suggests that Zta may also regulate the expression of
cellular genes. While many targets of Zta have been identified in the
Epstein-Barr virus genome, putative host cell targets remain largely
unknown. To address this issue, a tetracycline-regulated Zta expression
system was generated, and differential hybridization screening was used
to isolate Zta-responsive cellular genes. The major target identified by
this analysis is a gene encoding a fasciclin-like secreted factor,
transforming growth factor beta igh3 (TGF-beta igh3), that was
originally identified as a gene that is responsive to the potent
immunosuppressor TGF-beta 1. Northern (RNA) blot analysis demonstrated
that induction of Zta expression results in a 10-fold increase in
TGF-beta igh3 mRNA levels. Zta was also found to increase TGF-beta 1
mRNA levels as well as the amount of active TGF-beta 1 secreted into the
medium. Interestingly, alpha 1-collagen IV, which has been shown to
potentiate the effects of TGF-beta 1, is also a cellular target of Zta.
These results suggest that Zta could play a role in modulating the host
cell environment through activating the expression of secreted factors.
Mesh Headings
Unique Identifier: 95287473
Chemical Identifiers (Names)