Human immunodeficiency virus 1 Tat protein (HIV-1 Tat (Tat))

HIV-1 Tat is a small, basic, two-exon regulatory protein (~86–104 amino acids; ~9–16 kDa) that is essential for efficient transcription of the HIV-1 genome. Tat binds the trans-activation response element (TAR) at the 5′ end of nascent viral transcripts via its arginine-rich basic domain and recruits host P-TEFb (CDK9–cyclin T1), which hyperphosphorylates RNA polymerase II to drive productive elongation and full-length viral RNA synthesis. Structural work shows Tat forms a complementary interface with P-TEFb, contacting cyclin T1 and the CDK9 T-loop, and induces conformational changes enabling elongation; this interface is a target for inhibitor design. Tat contains multiple functional regions: an N-terminal proline-rich segment, a cysteine-rich motif, a hydrophobic core, an arginine-rich RNA-binding/basic domain (which also serves as a nuclear localization and protein transduction domain), and a variable C-terminus that includes an RGD motif implicated in integrin interactions and pathogenesis in vivo. Tat is also secreted from infected cells, crosses membranes, and is taken up by bystander cells, where it can dysregulate cellular pathways and contribute to CNS and systemic toxicity, making it both essential for replication and a contributor to HIV pathogenesis.

Other names

HIV-1 TatTrans-activator of transcription (Tat)Tat proteinTat (HIV)

Inhibitors aim to block Tat binding to TAR RNA, preventing recruitment of P-TEFb and thereby suppressing transcriptional elongation from the HIV-1 promoter. Inhibitors targeting the Tat·P-TEFb interface disrupt Tat-induced conformational changes and P-TEFb activation of RNA Pol II elongation. Neutralization of extracellular Tat to mitigate bystander toxicity and tissue damage.