AN INTERFERON REGULATORY FACTOR-BINDING SITE IN THE U5 REGION OF THE BOVINE LEUKEMIA-VIRUS LONG TERMINAL REPEAT STIMULATES TAX-INDEPENDENT GENE-EXPRESSION

Bovine leukemia virus (BLV) replication is controlled by both cis-and trans-acting elements. The virus-encoded transactivator, Tax, is neces sary for efficient transcription from the BLV promoter, although it is not present during the early stages of infection. Therefore, sequence s that control Tax-independent transcription must play an important ro le in the initiation of viral gene expression. This study demonstrates that the R-U5 sequence of BLV stimulates Tax-independent reporter gen e expression directed by the BLV promoter. R-U5 was also stimulatory w hen inserted immediately downstream from the transcription initiation site of a heterologous promoter. Progressive deletion analysis of this region revealed that a 46-bp element corresponding to the 5' half of U5 is principally responsible for the stimulation. This element exhibi ted enhancer activity when inserted upstream or downstream from the he rpes simplex virus thymidine kinase promoter. This enhancer contains a binding site for the interferon regulatory factors IRF-1 and IRF-2. A 3-bp mutation that destroys the IRF recognition site caused a twofold decrease in Tax-independent BLV long terminal repeat-driven gene expr ession. These observations suggest that the IRF binding site in the U5 region of BLV plays a role in the initiation of virus replication.