Human immunodeficiency virus type 1 Rev–Rev Response Element complex (HIV-1 Rev–RRE) (HIV-1 Rev–RRE)

The Human immunodeficiency virus type 1 Rev–Rev Response Element (HIV-1 Rev–RRE) complex is a critical ribonucleoprotein assembly consisting of the viral Rev protein and the Rev Response Element (RRE), a highly structured ~350-nucleotide RNA sequence located within the env gene [1.1.1, 1.2.2]. Its primary biological function is to facilitate the nucleocytoplasmic export of unspliced and partially spliced viral mRNAs, which are otherwise retained in the nucleus by host cell surveillance mechanisms that prevent the export of intron-containing transcripts [1.2.1, 1.2.3]. By binding to the RRE and multimerizing into a functional oligomer, Rev recruits host factors such as CRM1 and Ran-GTP to transport these essential transcripts to the cytoplasm for translation into structural proteins or packaging into new virions [1.1.3, 1.2.4]. In the context of disease, the Rev–RRE axis is indispensable for the late phase of the viral life cycle and has been linked to viral fitness, CD4+ T-cell decline, and the regulation of viral latency and reactivation [1.1.3, 1.4.3]. Although it is a highly attractive therapeutic target due to its essentiality and viral specificity, no Rev–RRE inhibitors are currently approved for clinical use [1.3.1, 1.5.1]. Experimental agents such as aminoglycosides (e.g., Neomycin B), benzofluorenones (e.g., Benfluron), and various peptides or RNA decoys have been studied for their ability to disrupt this interaction and inhibit HIV-1 replication [1.3.2, 1.5.2].

Other names

Rev-RRE regulatory axisRev-RRE systemRev-RRE ribonucleoprotein complexRev-RRE axisHIV-1 Rev-RRE complex

Inhibitors of the HIV-1 Rev–RRE complex typically function by disrupting the binding of the Rev protein to the Rev Response Element (RRE) RNA, preventing Rev multimerization, or blocking the recruitment of host export factors like CRM1, thereby halting the nuclear export of essential viral mRNAs [1.1.2, 1.3.1, 1.5.2].