title: [Establishment and application of a screening anti-HIV-1 drug model targeted nuclear trafficking of virus RNA].
abstract: 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.
authors.affiliation: Department of Immunology, Institute of Medicinal Biotechnology, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100050, China.
authors.forename: Zhen-long
authors.initials: ZL
authors.lastname: Liu
authors.forename: Xiao-yu
authors.initials: XY
authors.lastname: Li
authors.forename: Quan
authors.initials: Q
authors.lastname: Zhang
authors.forename: Ping-ping
authors.initials: PP
authors.lastname: Jia
authors.forename: Liang
authors.initials: L
authors.lastname: Yang
authors.forename: Xiao-lu
authors.initials: XL
authors.lastname: Wei
authors.forename: Jian-dong
authors.initials: JD
authors.lastname: Jiang
authors.forename: Shan
authors.initials: S
authors.lastname: Cen
mesh_terms: D021581:Active Transport, Cell Nucleus / Q000187:drug effects*; D019380:Anti-HIV Agents / Q000494:pharmacology*; D002467:Cell Nucleus / Q000378:metabolism*; D003062:Codon; D005231:Fatty Acids, Unsaturated / Q000494:pharmacology; D017930:Genes, Reporter; D049452:Green Fluorescent Proteins / Q000235:genetics / Q000378:metabolism; D057809:HEK293 Cells; D015497:HIV-1 / Q000187:drug effects / Q000235:genetics; D057166:High-Throughput Screening Assays; D006801:Humans; D028884:Karyopherins / Q000235:genetics / Q000378:metabolism; D012367:RNA, Viral; D018160:Receptors, Cytoplasmic and Nuclear / Q000235:genetics / Q000378:metabolism; D014162:Transfection; D014779:Virus Replication / Q000187:drug effects; D054321:rev Gene Products, Human Immunodeficiency Virus / Q000235:genetics / Q000378:metabolism; D000097606:Exportin 1 Protein
chemical_list: D019380:Anti-HIV Agents; D003062:Codon; D005231:Fatty Acids, Unsaturated; D049452:Green Fluorescent Proteins; D028884:Karyopherins; D012367:RNA, Viral; D018160:Receptors, Cytoplasmic and Nuclear; D054321:rev Gene Products, Human Immunodeficiency Virus; D000097606:Exportin 1 Protein; C514860:rev protein, Human Immunodeficiency Virus-1; C038753:leptomycin B