HIVbio: HIV Bioinformatics
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HIV Life Cycles
HIV Imp Enzymes
Drugs : HAART
Therapeutics and Vaccines
HIV Structural LandmarksThe RNA genome consists of at least seven structural landmarks (LTR,TAR, RRE, PE, SLIP, CRS, and INS) and nine genes(gag, pol, and env, tat, rev, nef, vif, vpr, vpu, and tev) encoding 19 proteins.
Long Terminal Repeats (LTR)
The Long Terminal Repeat is something which is often found in strands of RNA or DNA is the Long Terminal Repeat. At each end of the string is the same sequence of code at each end of the string. Almost like the repeat at the start and finish of these sentences, almost like!
There are two important functions for the LTR:
* Firstly they are "sticky ends" (that's a biochemistry term) which the integrase protein uses to insert the HIV genome into host DNA.
* Secondly, they act as promoter/enhancers - when integrated into the host genome, they influence the cell machinery which transcribes DNA, to alter the amount of transcription which occurs. Protein binding sites in the LTR are involved with RNA initiation.
In other words, Regulatory sequences important for viral replication that are located on each end of the HIV genome. The LTR includes the HIV ENHANCER, promoter, and other sequences. Specific regions in the LTR include the negative regulatory element (NRE), NF-kappa B binding sites , Sp1 binding sites, TATA BOX, and trans-acting responsive element (TAR). The binding of both cellular and viral proteins to these regions regulates HIV transcription.
Trans-Acting Responsive Element (TAR)
The HIV protein tat is necessary for the transcription of HIV DNA, for the simple reason that without it, the "trans-activating response region" or TAR mucks things up.
The TAR is found in the Long Terminal Repeat of HIV RNA/DNA. It's present in all mRNA transcripts and prevents the efficient use of the mRNA. tat binds to the RNA version of TAR and cancels its effect, allowing the mRNA to be efficiently processed into protein.
The TAR regions of HIV-1 and HIV-2 are different (HIV-1 TAR is pictured below) - but the conserved CUGGGA loop (at the top of the diagram), as well as the bulge just a little way down from that, has been shown to be essential for the trans-activation response.
* Position in genome: just at the start of the genome, after the 3' LTR.
* HIV can be inhibited experimentally by using TAR-RNA decoys.
Rev Response Element (RRE)
The Rev response element (RRE) is a region in the RNA molecule of the HIV env gene. Rev has a nuclear export signal and is essential for the export of the viral RNA out of the nucleus. snRNAs have a nuclear retention signal and prevent unspliced RNA from being exported out of the nucleus. Rev with its nuclear export signal can overcome this nuclear retention signal and thus allows for the export of the RNA even if its introns aren't spliced out.
Psi elements, a set of 4 stem-loop structures preceding and overlapping the Gag start codon. PE are the sites recognized by the cysteine histidine box, a conserved motif with the canonical sequence CysX2CysX4HisX4Cys, present in the Gag p7 MC protein. The Psi Elements are present in unspliced genomic transcripts, but absent from spliced viral mRNAs.
SLIP A TTTTTT slippery site, followed by a stem-loop structure, is responsible for regulating the -1 ribosomal frameshift out of the Gag reading frame into the Pol reading frame.
Cis-acting repressive sequences postulated to inhibit structural protein expression in the absence of Rev. One such site was mapped within the pol region of HIV-1. The exact function has not been defined; splice sites have been postulated to act as CRS sequences.
Inhibitory/Instability RNA sequences found within the structural genes of HIV-1 and of other complex retroviruses. Multiple INS elements exist within the genome and can act independently; one of the best characterized elements spans nucleotides 414 to 631 in the gag region of HIV-1. The INS elements have been defined by functional assays as elements that inhibit expression posttranscriptionally. Mutation of the RNA elements was shown to lead to INS inactivation and up-regulation of gene expression.