HIV-1 Rev protein (Rev)

The **HIV-1 Rev protein** is a ~13 kDa regulatory protein expressed from a fully spliced HIV-1 mRNA, composed of 116 amino acids[3][4][5]. Rev is essential for HIV-1 replication; it binds a highly structured cis-acting RNA element within viral RNAs called the Rev Response Element (RRE), oligomerizing on the RNA through its arginine-rich RNA-binding motif and additional self-association interfaces. Rev’s main function is to mediate the **nuclear export of unspliced and incompletely spliced HIV-1 RNA**—transcripts necessary for the synthesis of structural proteins (Gag, Pol, Env) and for packaging viral genomes[1][5][6][7]. The protein shuttles between the nucleus and cytoplasm using its nuclear localization and export signals (NLS and NES), recruiting the host's Crm1/exportin-1 pathway to export RRE-containing viral RNAs. Rev also participates, less well-characterized, in regulating RNA splicing, stability, and translation[4][5][7]. Rev assembles as multimers (typically tetramers or higher order) on the RRE, with structural studies detailing its anti-parallel helix-turn-helix fold and self-association interfaces (A–A, B–B, and C–C interactions)[2][5][8]. The essential role of Rev in HIV-1 replication makes it a key therapeutic target, though to date, no direct Rev inhibitors have been approved for clinical use. Efforts include targeting its RNA interactions, oligomerization, or the protein-protein interfaces required to assemble its RNA-export complex[2][5].

Other names

Regulator of expression of virion proteinsRev (HIV)HIV RevTRS/ART (historic/early naming)

Drugs or inhibitors targeting Rev would generally block Rev-RRE binding and oligomerization, or Rev’s interaction with export receptors, thereby preventing nuclear export of viral RNAs and blocking late-stage viral protein expression and viral replication[1][2][5][7].