trans-acting regulation of bovine leukemia virus mRNA processing

Bovine leukemia virus (BLV) and the human T-cell leukemia virus types I and II comprise a unique retrovirus subfamily which has evolved complex strategies for the regulation of gene expression. A transcriptional control circuit has been characterized in both human and bovine systems in which cis-acting promoter control elements are responsive to trans-acting factors encoded in the pX region of the virus. The BLV pX mRNA encoding the transcriptional trans-acting factor is translated in an alternate reading frame to produce an 18-kilodalton nuclear phosphoprotein, p18. A function for this protein was revealed in cotransfection experiments using mutated BLV proviruses in combination with pX expression plasmids. These experiments indicated that p18 was required for the accumulation of viral mRNAs representing full-length (genomic) and single-spliced (env) transcripts. In contrast, synthesis of the double-spliced pX mRNA was not influenced by p18 expression. Large regional deletions and substitutions of provirus sequences localized elements essential for p18 regulation to the 3' long terminal repeat. Furthermore, sequences within a 250-nucleotide region between the AATAAA signal and poly(A) site were found to be essential for efficient virus mRNA 3'-end processing and response to p18 regulation.