Note: this site last updated in 2006
Protein binding sites in the LTR
An article from "The Molecules of HIV" (c) Dan Stowell
LTR.gif" alt="Diagram illustrating consensus binding sites" />
In the diagram, the numbers represent the position in the "reading frame" when the DNA is being transcribed - the cellular & viral machinery starts working at +1 and moves upwards, through +95 and onwards. You can see that most of the LTR is therefore not transcribed. The LTR has its effect because proteins bind to it, influencing whether or not RNA is to be produced from the section of the cellular DNA which is proviral.
The NFkB and NFAT-1 sites are important because they recognise proteins that bind to DNA when T cells are activated. In resting T cells very little, if any, RNA is made. In an activated T cell, however, proteins bind to the NFkB & NFAT-1 sites, allowing proviral transcription to begin. Hence the viral machinery goes into production.
The Negative Regulatory Element (NRE) takes up much of the LTR, and is known to contain sequences which suppress initiation of transcription. Deleting the NRE yields virus strains which produce five times as much virus in T cell lines. An NRE is not found in many other retroviruses">retroviruses - it is part of the machinery that allows HIV to lie low in host cells.