Epstein-Barr virus bicistronic mRNAs generated by facultative splicing code for two transcriptional trans-activators

Abstract

The Epstein-Barr virus (EBV) genome codes for several transcriptional trans-activators. One of them, the BZLF1 open reading frame (ORF)-encoded product EB1, is able to induce the productive cycle in infected B cells. From the cloning and characterization of full-length cDNAs, we found that EB1 could be made from three overlapping messenger RNAs expressed under the control of two different promoters that we call P1 and P2. The first mRNA, 1 kb long, is made from the P1 promoter and codes for EB1 alone. The two other mRNAs, respectively 3 and 4 kb long and made by facultative splicing, are bicistronic mRNAs. They code not only for the trans-activator EB1 but also for a second EBV transcriptional trans-activator R, encoded by the BRLF1 ORF. In effect, authentic EB1 and R proteins are expressed from the 3 and 4 kb long cDNAs as demonstrated by identification of the proteins with specific antisera. In addition, EB1 and R expressed from the 3 and 4 kb cDNAs activate transcription from their specific targets in the EBV early promoter DR.