Human immunodeficiency virus type 1 trans-activation response element (HIV-1 TAR element) (HIV-1 TAR element)

The HIV-1 trans-activation response (TAR) element is a 59-nucleotide RNA stem-loop structure located at the 5' end of all nascent HIV-1 transcripts (Karn & Stoltzfus, 2012, PMID: 22403101). It is encoded within the long terminal repeat (LTR) and serves as the essential binding site for the viral trans-activator protein, Tat (Bannwarth & Gatignol, 2005, PMID: 15638720). Upon binding, Tat recruits the host positive transcription elongation factor b (P-TEFb) complex, which phosphorylates the C-terminal domain of RNA polymerase II. This process converts the polymerase from a non-processive to a highly processive form, enabling the efficient elongation of viral mRNA. Without the TAR-Tat interaction, HIV-1 transcription is severely restricted, resulting in short, non-functional transcripts. Because of its critical role in viral replication and its highly conserved sequence, the TAR element is a significant target for antiviral drug development. Therapeutic strategies include small molecules and peptidomimetics designed to competitively inhibit Tat binding or disrupt the recruitment of host transcriptional machinery (Mousseau et al., 2015, PMID: 26361154). Targeting TAR is also explored in the context of block and lock strategies to enforce permanent viral latency.

Other names

TAR RNATrans-activation response elementHIV-1 TARTAR hairpinHIV-1 TAR element

Inhibition of Tat-TAR binding and disruption of P-TEFb recruitment to the viral promoter