Human immunodeficiency virus type 1 Rev–Rev response element interaction (HIV-1 Rev–RRE interaction)

The Human immunodeficiency virus type 1 (HIV-1) Rev–Rev response element (RRE) interaction is a fundamental regulatory mechanism required for the export of unspliced and singly spliced viral mRNA from the nucleus to the cytoplasm (Pollard & Malim, 1998, PMID: 9630223). The viral protein Rev binds specifically to the RRE, a highly structured 351-nucleotide RNA segment located within the viral env gene (Zapp et al., 1993, PMID: 7683061). Upon binding, Rev undergoes multimerization and recruits the host nuclear export receptor CRM1 (Exportin-1), facilitating the transport of essential viral transcripts that encode structural proteins and the viral genome itself (Fernandes et al., 2012, PMID: 22403173). This interaction is indispensable for the late phase of the HIV-1 life cycle, as the absence of Rev-mediated export leads to the degradation of these transcripts or their retention in the nucleus (Dayton, 2004, PMID: 15141623). As a highly conserved and essential process, the Rev–RRE interaction serves as an attractive target for the development of next-generation antiretroviral therapies, particularly for patients harboring multi-drug resistant viral strains (Jayaraman et al., 2014, PMID: 25151341). Current research focuses on small molecules, peptides, and aptamers designed to disrupt this protein-RNA interface and inhibit viral replication (Sherpa et al., 2015, PMID: 25607358).

Other names

Rev-RRE complexHIV-1 Rev-RRE axisRev-RRE systemRegulator of expression of virion proteins-Rev response element interaction

Inhibition of the Rev protein binding to the RRE RNA structure, prevention of Rev multimerization on the RNA, or blocking the recruitment of the host export protein CRM1, thereby preventing the nuclear export of unspliced and singly spliced viral transcripts.