HIV-1 Regulator of expression of virion proteins (Rev) (Rev)

The HIV-1 Regulator of expression of virion proteins (Rev) is a critical 116-amino acid phosphoprotein essential for the replication of the Human Immunodeficiency Virus type 1 (HIV-1) (UniProt: P04618). Its primary biological role is to mediate the nuclear export of unspliced and singly spliced viral mRNAs, which are necessary for the synthesis of viral structural proteins and the packaging of the viral genome (PubMed: 22541217). Rev functions by recognizing and binding to a complex secondary RNA structure called the Rev Response Element (RRE) found within the viral transcripts. Following binding, Rev undergoes multimerization and utilizes its nuclear export signal (NES) to recruit the host cell's exportin-1 (CRM1) protein, facilitating transport through the nuclear pore complex (PubMed: 29334312). Because Rev is indispensable for the production of new virions, it represents a significant therapeutic target for antiretroviral therapy. Although various small molecules, such as PKF050-638, and RNA-based aptamers have been developed to inhibit Rev-RRE interaction or Rev multimerization, none have yet reached clinical approval (PubMed: 15618531). A major challenge in targeting Rev is the potential for toxicity if the drug interferes with the host's endogenous CRM1-mediated nuclear export of essential cellular proteins and RNAs (PubMed: 25634373). Additionally, the high mutation rate of HIV-1 poses a risk for the rapid development of resistance against Rev-targeted inhibitors.

Other names

Rev proteinRegulator of expression of virion proteinsHIV-1 Revp19 Rev

Inhibition of Rev-RRE binding, disruption of Rev multimerization, or blockade of the Rev-CRM1 nuclear export pathway.