Regulator of expression of virion proteins (Rev) (Rev)

HIV-1 Rev (Regulator of expression of virion proteins) is an essential 116-amino acid regulatory protein required for the replication of the human immunodeficiency virus type 1 (HIV-1) [1, 5]. It acts as a nucleocytoplasmic shuttle protein that facilitates the export of unspliced and singly spliced viral mRNAs from the host cell nucleus to the cytoplasm [1, 6]. This function is vital for the viral life cycle because these "late" transcripts, which encode essential structural proteins such as Gag, Pol, and Env, would otherwise be retained and degraded in the nucleus [1, 11]. Rev functions by binding to the Rev Response Element (RRE), a complex RNA structure within the viral genome, where it multimerizes and recruits the host nuclear export receptor CRM1 (XPO1) to transport the viral ribonucleoprotein complex [5, 12]. In clinical terms, Rev is a critical driver of the transition from early to late viral gene expression and is significantly involved in the maintenance and reactivation of viral latency [4, 21]. While there are currently no FDA-approved drugs that directly target Rev, it remains a major focus for drug development due to its indispensable role in viral production [2, 6]. Therapeutic candidates under investigation include small molecules that disrupt the Rev-RRE or Rev-CRM1 interactions, as well as splicing modulators like Obefazimod (ABX464) that indirectly reduce Rev levels [1, 4]. Key challenges in targeting Rev include the high potential for viral resistance through compensatory mutations and the risk of toxicity associated with inhibiting host-cell nuclear export pathways [2, 20].

Other names

Protein RevARTTRSAnti-repression transactivatorp19Regulator of expression of viral proteins

Inhibition of the Rev-RRE interaction, disruption of Rev multimerization, blockade of the Rev-CRM1 (XPO1) nuclear export pathway, or modulation of viral RNA splicing to reduce Rev expression.