HIV-1 Regulator of expression of virion proteins (Rev) – Rev-responsive element (RRE) nuclear export complex (Rev-RRE complex)

The HIV-1 Rev – Rev-responsive element (RRE) nuclear export complex is a vital ribonucleoprotein assembly essential for the replication of the human immunodeficiency virus type 1 (HIV-1) [1, 3]. This complex forms when multiple molecules of the viral Rev protein bind to the RRE, a highly structured RNA element found within the env gene of unspliced and partially spliced viral transcripts [3, 7]. Its primary biological function is to bypass the host cell's nuclear retention of intron-containing RNAs by recruiting the host exportin CRM1 (XPO1) and Ran-GTP, thereby facilitating the export of these mRNAs to the cytoplasm for translation and virion assembly [7, 12, 15]. In the context of disease, the Rev-RRE axis is a critical checkpoint in the HIV-1 life cycle; its failure leads to a complete block in the production of structural proteins and infectious progeny [2, 12]. As a therapeutic target, the Rev-RRE complex offers high viral specificity, potentially reducing side effects compared to host-targeted therapies [4, 14]. Various experimental drugs have been developed to disrupt this complex, including small molecules like benfluron that interfere with Rev-RRE binding, and aminoglycosides like neomycin that bind the RNA scaffold [2, 4, 14]. Other strategies involve inhibiting the recruitment of host factors, as seen with the CRM1 inhibitor leptomycin B, or preventing Rev's entry into the nucleus using ivermectin [2, 14, 15]. Despite its promise, no drugs targeting this complex are currently approved, primarily due to challenges such as cellular toxicity and the rapid emergence of viral resistance mutations [2, 6, 15].

Other names

Rev-RRE axisRev-RRE regulatory axisRev-RRE ribonucleoprotein complexRev-RRE-CRM1 complexRev-RRE-XPO1 complexRev-RRE export complex

Inhibition of Rev-RRE binding, Rev oligomerization, or CRM1-mediated nuclear export to prevent the transport of intron-containing viral mRNAs to the cytoplasm [2, 4, 5, 15].