Figure 1.

The HIV-rtTA genome and mutations in the TAR hairpin. (A) The HIV-rtTA proviral DNA genome and the viral RNA transcript are shown. In this virus the Tat-TAR axis of transcription regulation was inactivated by mutation of both Tat and TAR (tat^m and TAR^m; crossed boxes) and functionally replaced by the doxycycline(dox)-inducible Tet-ON gene regulation system [32,33]. The tetO elements were introduced in the U3 promoter region and the Nef gene was replaced by the rtTA gene. The R region that is present at both the 5' and 3' end of the viral transcript folds the TAR and polyA hairpin elements. The latter structure is truncated upon polyadenylation at the 3' R. (B) The wild-type TAR hairpin (TAR^wt) and the TAR^m version with bulge and loop mutations as present in the HIV-rtTA virus are shown. The TAR^m sequence is partially deleted in the mutants A, B and AB. The deleted nucleotides are indicated by a grey box. The transcription and replication properties of these mutant viruses are indicated as previously presented [34,35].