Fig. 1

Schematic representation of the BLV genome. The BLV proviral genome is flanked by two identical Long Terminal Repeats (the 5ʹLTR and the 3ʹLTR). The 5ʹLTR contains the core RNAPII promoter elements (CAAT and TATA boxes) and associated cis-regulatory elements (see text) responsible for the expression of 5ʹ-capped unspliced (Genomic), single-spliced (Env, G4) or multi-spliced (Tax/Rex, R3) sense transcripts, each coding for different viral proteins. Through interactions with the cellular CREB, CREM, ATF-1 and ATF-2 transcription factors, the viral protein Tax transactivates the 5ʹLTR sense promoter activity. The miRNA region is composed of a cluster of 5 independent RNAPIII promoters, each containing characteristic type 2 RNAPIII promoter elements (A-like Box, B-like Box) and a terminator and is responsible for the constitutive expression of 5 pre-miRNAs (pre-miRNA-B1 to− B5) independently of Drosha. The pre-miRNAs are further processed by Dicer in 10 viral miRNAs (miR-B1-5p and 3p to miR-B5-5p and 3p). The 3’LTR exhibits a TATA-less antisense RNAPII promoter that operates thanks to a combination of core promoter elements (MTE, DPE, BRE) and different cis-regulatory elements (IRF, E-Box 4) and that is responsible for the expression of 3 single-spliced antisense transcripts (AS1-S, AS1-L, AS2) initiated from two major transcription start sites. Although the LTRs are identical, only cis-regulatory elements with known impact on sense or antisense promoter activity are represented in the 5ʹLTR or 3ʹLTR, respectively. Sequences of the described cis-regulatory elements can be found in Annex 1