Human immunodeficiency virus type 1 regulatory proteins (Tat and Rev) (HIV-1 Tat/Rev)

Human immunodeficiency virus type 1 (HIV-1) regulatory proteins, specifically Tat (Trans-activator of transcription) and Rev (Regulator of expression of virion proteins), are essential components of the viral replication cycle. Tat significantly increases the processivity of RNA polymerase II by binding to the trans-activation response (TAR) RNA element, thereby driving high-level viral gene expression (UniProt P04608). Rev is responsible for the nuclear export of unspliced and partially spliced viral transcripts by binding to the Rev response element (RRE), a process necessary for the synthesis of structural proteins and the packaging of the viral genome (PubMed: 25101140). Because these proteins are indispensable for viral production and are not present in the host genome, they represent attractive therapeutic targets for "block-and-lock" strategies aimed at achieving a functional cure. Current research focuses on small molecules and RNA-based inhibitors that disrupt the interaction between these proteins and their respective viral RNA elements or host co-factors (PubMed: 22745331, PubMed: 30104374). Despite their potential, the high mutation rate of HIV-1 and the intrinsically disordered nature of Tat pose significant hurdles for the development of stable, long-term clinical therapies.

Other names

HIV-1 TatHIV-1 RevTrans-activator of transcriptionRegulator of expression of virion proteinsp14p19

Inhibition of Tat-mediated transcriptional transactivation and Rev-mediated nuclear export of viral mRNA.