Establishment and application of a screening anti-HIV-1 drug model targeted nuclear trafficking of virus RNA.
- Author:
Zhen-long LIU
1
;
Xiao-yu LI
;
Quan ZHANG
;
Ping-ping JIA
;
Liang YANG
;
Xiao-lu WEI
;
Jian-dong JIANG
;
Shan CEN
Author Information
1. Department of Immunology, Institute of Medicinal Biotechnology, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100050, China.
- Publication Type:Journal Article
- MeSH:
Active Transport, Cell Nucleus;
drug effects;
Anti-HIV Agents;
pharmacology;
Cell Nucleus;
metabolism;
Codon;
Fatty Acids, Unsaturated;
pharmacology;
Genes, Reporter;
Green Fluorescent Proteins;
genetics;
metabolism;
HEK293 Cells;
HIV-1;
drug effects;
genetics;
High-Throughput Screening Assays;
Humans;
Karyopherins;
genetics;
metabolism;
RNA, Viral;
Receptors, Cytoplasmic and Nuclear;
genetics;
metabolism;
Transfection;
Virus Replication;
drug effects;
rev Gene Products, Human Immunodeficiency Virus;
genetics;
metabolism
- From:
Acta Pharmaceutica Sinica
2010;45(2):257-262
- CountryChina
- Language:Chinese
-
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.
