RESUMO
The HIV-1 Rev protein facilitates nuclear export of unspliced and singly spliced viral transcripts containing RRE RNA through the CRM1 export pathway. Inhibition of Rev-mediated RNA nuclear export can arrest HIV-1 transcriptional process, which clearly, reveals a target for anti-HIV drug development. In this work, a cell-based assay has been established for screening anti-HIV compounds targeting the Rev-mediated RNA nuclear export. This assay utilized a codon-optimized green fluorescent protein (GFP) as reporter gene, which expression is in a Rev-dependent manner. Any compound that inhibits the Rev-mediated RNA nuclear export is identified by reducing emission of GFP. The Z' score of this model is 0.8220. Three thousands compounds were screened and the positive rate was 9.3% with a cutoff at 50% inhibition. IMB7C7, one of the positive compounds, efficiently inhibits viral production from HIV-1 infected cells.
Assuntos
Humanos , Transporte Ativo do Núcleo Celular , Fármacos Anti-HIV , Farmacologia , Núcleo Celular , Metabolismo , Códon , Ácidos Graxos Insaturados , Farmacologia , Genes Reporter , Proteínas de Fluorescência Verde , Genética , Metabolismo , Células HEK293 , HIV-1 , Genética , Ensaios de Triagem em Larga Escala , Carioferinas , Genética , Metabolismo , RNA Viral , Receptores Citoplasmáticos e Nucleares , Genética , Metabolismo , Transfecção , Replicação Viral , Produtos do Gene rev do Vírus da Imunodeficiência Humana , Genética , MetabolismoRESUMO
HIV-1 Rev is an indispensable regulatory factor of the virion protein expression. The interaction between Rev and RRE RNA accelerates the nuclear export of viral mRNA. The unspliced and singly spliced mRNA will be degraded in the absence of Rev, resulting in the interception of HIV-1 replication at the same time. The pivotal role that Rev plays in HIV-1 replication as a trans-acting factor makes it a new target in the research of AIDS drugs. In this review, the function of Rev, Rev-RRE interaction, as well as their related inhibitors are reported.
Assuntos
Transporte Ativo do Núcleo Celular , Sequência de Aminoácidos , Fármacos Anti-HIV , Química , Farmacologia , Núcleo Celular , Metabolismo , Ácidos Graxos Insaturados , Química , Farmacologia , Framicetina , Química , Farmacologia , HIV-1 , Genética , Metabolismo , Fisiologia , Carioferinas , Metabolismo , RNA Mensageiro , Genética , RNA Viral , Genética , Receptores Citoplasmáticos e Nucleares , Metabolismo , Transcrição Gênica , Replicação Viral , Produtos do Gene rev do Vírus da Imunodeficiência Humana , MetabolismoRESUMO
Nucleocytoplasmic transport of proteins occurs through pores embedded in the nuclear envelope. Recent studies have defined the cytoplasmic factors required for signal-mediated import of nuclear proteins. Considerable progress has been made in understanding the mechanism of nuclear export of proteins by the identification of specific signal sequences needed for export. Regulatory molecules have been shown to adopt novel mechanisms to control their entry into the nucleus and thereby regulate their functions.