Natural sequence variation of the HIV core promoter. (A) The HIV genome is shown in schematized form. The gene encoding the viral trans-activating protein, Tat, is in black. The core promoter of the 5’ long terminal repeat (LTR) is in blue. (B) A schematized version of the HIV promoter (5’ LTR) is shown with cellular transcription factors in grey. Viral Tat protein is shown in black interacting with the TAR stem-loop RNA structure at the 5’ end of the nascent HIV transcript. The TATA box and adjacent sequences of HIV essential for Tat trans-activation (TASHET) contain the TATA box (purple) and flanking sequences (blue). A question mark highlights a mechanistic missing link in our current understanding of the specific requirement for TASHET in Tat trans-activation. (C) Natural sequence variation of TASHET (positions – 35 to – 14 relative to the transcription start site) is shown. HIV sequences from the Los Alamos HIV Sequence Database (http://www.hiv.lanl.gov) were aligned, and the weblogo algorithm (http://weblogo.berkeley.edu/) was used to generate a logo sequence in which the height of each nucleotide position indicates sequence conservation. The height of different nucleotides at single position indicates their relative frequency.