Open AccessThe bZIP Transactivator of Epstein-Barr Virus, BZLF1, Functionally and Physically Interacts with the p65 Subunit of NF-kB
Author(s) -
David Gutsch,
Elizabeth Holley-Guthrie,
Q Zhang,
Bernd Stein,
Michael A. Blanar,
Albert S. Baldwin,
Shan C. Kenney
Publication year - 1994
Publication title -
molecular and cellular biology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.14
H-Index - 327
eISSN - 1067-8824
pISSN - 0270-7306
DOI - 10.1128/mcb.14.3.1939-1948.1994
Subject(s) - transactivation , biology , bzlf1 , immunoprecipitation , promoter , transcription factor , microbiology and biotechnology , cell culture , virology , virus , gene , gene expression , genetics , viral disease , herpesviridae
The Epstein-Barr virus (EBV) BZLF1 (Z) immediate-early transactivator initiates the switch between latent and productive infection in B cells. The Z protein, which has homology to the basic leucine zipper protein c-Fos, transactivates the promoters of several replicative cycle proteins. Transactivation efficiency of the EBV BMRF1 promoter by Z is cell type dependent. In B cells, in which EBV typically exists in a latent form, Z activates the BMRF1 promoter inefficiently. We have discovered that the p65 component of the cellular factor NF-kappa B inhibits transactivation of several EBV promoters by Z. Furthermore, the inhibitor of NF-kappa B, I kappa B alpha, can augment Z-induced transactivation in the B-cell line Raji. Using glutathione S-transferase fusion proteins and coimmunoprecipitation studies, we demonstrate a direct interaction between Z and p65. This physical interaction, which requires the dimerization domain of Z and the Rel homology domain of p65, can be demonstrated both in vitro and in vivo. Inhibition of Z transactivation function by NF-kappa B p65, or possibly by other Rel family proteins, may contribute to the inefficiency of Z transactivator function in B cells and may be a mechanism of maintaining B-cell-specific viral latency.