HIV-1 Rev response element RNA (RRE)

The HIV-1 Rev response element (RRE) is a complex, highly structured RNA sequence of approximately 350 nucleotides located within the viral envelope (env) gene (Dayton et al., 1989). It serves as a critical regulatory element in the HIV-1 life cycle by facilitating the nuclear export of unspliced and singly spliced viral mRNAs (Pollard and Malim, 1998). These mRNAs are essential for the production of structural proteins like Gag and Env, as well as the packaging of the viral genome. The export process is initiated when the viral Rev protein binds to a specific high-affinity site within the RRE, known as Stem-Loop IIB (Hoffman et al., 2012). Following binding, Rev multimerizes and recruits the host cellular export protein CRM1 to transport the RNA-protein complex out of the nucleus. Because this interaction is indispensable for viral replication, the RRE is a prominent target for the development of novel antiretroviral therapies. Various small molecules, including aminoglycosides like Neomycin B and synthetic terphenyl derivatives, have been shown to competitively inhibit the Rev-RRE interaction (Zapp and Green, 1989; Fernandes et al., 2012). Successfully targeting the RRE effectively traps essential viral transcripts in the nucleus, thereby preventing the assembly and release of new infectious virions. However, therapeutic development is challenged by the need for high specificity to avoid off-target binding to host cellular RNAs, such as ribosomal RNA.

Other names

RRERev-binding elementHIV-1 RRE

Inhibition of the Rev protein binding to the RRE, thereby preventing the CRM1-mediated nuclear export of unspliced and singly spliced viral transcripts.