The
HIV-1 LTR is 634 bp in length and, like other
retroviral LTRs, is segmented into the U3, R, and U5 regions. U3 and U5 has been further subdivided according to transcription factor sites and their impact on LTR activity and viral gene expression. The multi-step process of reverse transcription results in the placement of two identical LTRs, each consisting of a U3, R, and U5 region, at either end of the proviral DNA. The ends of the LTRs subsequently participate in integration of the provirus into the host
genome. Once the provirus has been integrated, the LTR on the 5′ end serves as the promoter for the entire retroviral genome, while the LTR at the 3′ end provides for nascent viral RNA
polyadenylation and, in HIV-1, HIV-2, and SIV, encodes the accessory protein,
Nef. All of the required signals for gene expression are found in the LTRs: Enhancer, promoter (can have both transcriptional enhancers or regulatory elements), transcription initiation (such as capping), transcription terminator and polyadenylation signal. In HIV-1, the
5'UTR region has been characterized according to functional and structural differences into several sub-regions: •
TAR, or
trans-activation response element, plays a critical role in transcriptional activation via its interaction with viral proteins. It forms a highly stable stem–loop structure consisting of 26 base pairs with a bulge in its secondary structure that interfaces with the viral transcription activator protein
Tat. •
Poly A plays roles both in
dimerization and genome packaging since it is necessary for cleavage and
polyadenylation. It has been reported that sequences upstream (U3 region) and downstream (U5 region) are needed in order to make the cleavage process efficient. •
PBS, or
primer binding site, is 18 nucleotides long and has a specific sequence that binds to the tRNALys primer required for initiation of reverse transcription. •
Psi (Ψ), or the
Psi packaging element, is a unique motif involved in regulating the packaging of the viral genome into the
capsid. It is composed of four stem-loop (SL) structures with a major splicing donor site embedded in the second SL. •
DIS, or dimer initiation site, is a highly conserved RNA–RNA interacting sequence constituting the SL1 stem–loop in the Psi packaging element of many retroviruses. DIS is characterized by a conserved stem and palindromic loop that forms a
kissing-loop complex between HIV-1 RNA genomes to dimerize them for
encapsidation. The transcript begins, at the beginning of R, is capped, and proceeds through U5 and the rest of the provirus, usually terminating by the addition of a poly A tract just after the R sequence in the 3' LTR. The finding that both HIV LTRs can function as transcriptional promoters is not surprising since both elements are apparently identical in nucleotide sequence. Instead, the 3' LTR acts in transcription termination and polyadenylation. However, it has been suggested that the transcriptional activity of the 5' LTR is far greater than that of the 3' LTR, a situation that is very similar to that of other retroviruses. ==See also==