Regulation of Epstein-Barr virus promoters in oral epithelial cells and lymphocytes.
Hairy leukoplakia (HL) is a proliferative lesion of the tongue that supports abundant Epstein-Barr virus (EBV) replication. Previous work showed high-level expression of the EBV BMRF2 gene in HL. To characterize the regulation of BMRF2 expression in HL, we mapped the 5' ends of the BMRF1 and BMRF2 transcripts and showed that BMRF2 is expressed from a novel internal promoter within the BMRF1 coding region. Mechanisms of BMRF2 regulation were compared in oral epithelial cells and B lymphocytes, as were those of BMRF1 and BDLF3, early and late EBV transcripts, respectively, that are also known to be expressed in HL. Basal activity of the putative BMRF2 promoter was 10-fold higher in HSC-3 epithelial cells than in B lymphocytes. The BMRF2 and the BDLF3 promoters were responsive to induction by phorbol ester, but unlike the BMRF1 promoter, they were not responsive to BZLF1 transactivation. By mutational analysis, the major activity of the BMRF2 promoter mapped to a 50-bp region, which includes a TATA-like element and a GC box. The BMRF2 promoter may be regulated differentially from the BMRF1 promoter and more closely resembles that of BDLF3. This novel BMRF2 promoter likely belongs to a class of viral promoters that is more responsive to mechanisms known to induce epithelial cell differentiation, consistent with its high level of expression in HL.
Departments of Stomatology, University of California, San Francisco, California, USA.
L A
LA
Lagenaur
J M
JM
Palefsky
D000956:Antigens, Viral / Q000235:genetics*; D001402:B-Lymphocytes / Q000821:virology*; D016207:Cytokines / Q000378:metabolism; D004847:Epithelial Cells / Q000821:virology; D016222:Fibroblast Growth Factor 2 / Q000378:metabolism; D015967:Gene Expression Regulation, Viral; D015696:Gene Products, tat / Q000378:metabolism; D004854:Herpesvirus 4, Human / Q000235:genetics*; D006801:Humans; D017733:Leukoplakia, Hairy / Q000473:pathology / Q000821:virology*; D008562:Membrane Glycoproteins / Q000235:genetics*; D009055:Mouth / Q000166:cytology / Q000821:virology*; D016296:Mutagenesis; D011401:Promoter Regions, Genetic; D016212:Transforming Growth Factor beta / Q000378:metabolism; D014407:Tumor Cells, Cultured; D014764:Viral Proteins / Q000235:genetics*
D000956:Antigens, Viral; C109483:BDLF-3 protein, Human herpesvirus 4; C109482:BMRF-2 protein, Human herpesvirus 4; D016207:Cytokines; C083204:Epstein-Barr virus early antigen diffuse component; D015696:Gene Products, tat; D008562:Membrane Glycoproteins; D016212:Transforming Growth Factor beta; D014764:Viral Proteins; D016222:Fibroblast Growth Factor 2