Transcription of the HIV genome

Transcription of the HIV genome Expression of the integrated HIV-1 provirus is dependent on the host cell Pol II transcription machinery, but is regulated in critical ways by HIV-1 Tat and Rev proteins. The long terminal repeats (LTR) located at either end of the proviral DNA contain regulatory sequences that recruit cellular transcription factors. The U3 region of the 5' LTR contains numerous cis-acting elements that regulate Pol II-mediated transcription initiation. The full-length transcript, which encodes nine genes, functions as an mRNA and is packaged as genomic RNA. Smaller (subgenomic) viral mRNAs are generated by alternative splicing. The activities of Tat and Rev create two phases of gene expression (see Karn 1999; Cullen 1991). The Tat protein is an RNA specific trans-activator of LTR-mediated transcription. Association of Tat with TAR, a RNA stem-loop within the RNA leader sequence, is required for efficient elongation of the HIV-1 transcript. In the early phase of viral transcription, a multiply-spliced set of mRNAs is generated, producing the transcripts of the regulatory proteins, Tat, Rev, and Nef. In the late phase, Rev regulates nuclear export of HIV-1 mRNAs, repressing expression of the early regulatory mRNAs and promoting expression of viral structural proteins. Nuclear export of the unspliced and partially spliced late HIV-1 transcripts that encode the structural proteins requires the association of Rev with a cis-acting RNA sequence in the transcripts (Rev Response Element, RRE).