THE EPSTEIN-BARR-VIRUS BRLF1 GENE-PRODUCT TRANSACTIVATES THE MURINE AND HUMAN C-MYC PROMOTERS

A common feature of the Epstein-Barr virus (EBV)-associated malignancy , Burkitt's lymphoma, is chromosomal translocation affecting the c-myc oncogene. We report here that an EBV immediate-early (IE) protein, BR LF1 (R), transactivates the murine and human c-myc promoters. The R tr ansactivator enhances expression from transiently transfected murine a nd human c-myc promoters as determined both at the CAT reporter and at the mRNA level. Transactivation of the human c-myc promoter by R occu rs in several different cell lines, and this effect is reporter-gene i ndependent. Both the P1 and P2 c-myc promoters can be activated by the EBV R IE protein, although the R-induced transactivation of P1 is gre ater than P2. The portion of the human c-myc promoter from -228 to -63 (relative to the P1 mRNA start site) is necessary, but not sufficient , for transactivation by R in the Louckes B-cell line. Binding of the R protein directly to the c-myc promoter could not be demonstrated, su ggesting that the effect of R on c-myc activity occurs by an indirect mechanism. The ability of an EBV protein to activate c-myc expression is likely to facilitate productive viral infection and is also potenti ally relevant in the genesis of EBV-associated lymphomas.