Regulation of Epstein-Barr virus promoters in oral epithelial cells and lymphocytes

Hairy leukoplakia (HL) is a proliferative lesion of the tongue that support s abundant Epstein-Barr virus (EBV) replication. Previous work showed high- level expression of the EBV BMRF2 gene in HL. To characterize the regulatio n of BMRF2 expression in HL,we mapped the 5' ends of the BMRF1 and BMRF2 tr anscripts and showed that BMRF2 is expressed from a novel internal promoter within the BMRF1 coding region. Mechanisms of BMRF2 regulation were compar ed in oral epithelial cells and B lymphocytes, as were those of BMRF1 and B DLF3, early and late EBV transcripts, respectively, that are also known to be expressed in BL. Basal activity of the putative BMRF2 promoter was 10-fo ld higher in HSC-3 epithelial cells than in B lymphocytes. The BMRF2 and th e BDLF3 promoters were responsive to induction by phorbol eater, 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 5 0-bp region, which includes a TATA-like element and a GC box. The BMRF2 pro moter may be regulated differentially from the BMRF1 promoter and more clos ely resembles that of BDLF3. This novel BMRF2 promoter likely belongs to a class of viral promoters that is more responsive to mechanisms known to ind uce epithelial cell differentiation, consistent with its high level of expr ession in HL.