Establishment of pharmacological evaluation system for non-nucleoside reverse-transcriptase inhibitors resistant HIV-1 / 药学学报
Acta Pharmaceutica Sinica
; (12): 355-361, 2009.
Article
in Zh
| WPRIM
| ID: wpr-278257
Responsible library:
WPRO
ABSTRACT
Consistent non-nucleoside reverse-transcriptase inhibitors (NNRTIs) resistant HIV-1 strains occurred due to the clinical use for more than ten years of efavirenz (EFV), nevirapine (NVP), and delavirdine (DLV). In this study, we established nine cell-based pharmacological models according to most NNRTIs-resistant clinical tested strains, Resistant mutations were introduced into vector, pNL4-3.Luc.R-E-, by overlapping PCR. Then, pseudovirions were produced by co-transfection of VSV-G plasmid and pNL4-3.Luc.R-E- -mut. All nine recombinant VSVG/HIV-mut pseudovirions (VSVG/HIV-wt, VSVG/HIV(-K103N), VSVG/HIV(-Y181C), VSVG/HIV(-L100I,K103N), VSVG/HIV(-Y188L), VSVG/HIV(-K103N,Y181C), VSVG/HIV(-K103N,P225H), VSVG/HIV(-K103N,Y188L), VSVG/HIV(-K103N,G109A) and VSVG/HIV(-K103N,V108I)) had high efficient infectivity. Furthermore, they all showed resistant characteristics to EFV and NVP with IC50 changes consisting with clinical reports, not to nucleoside reverse-transcriptase inhibitors (AZT and d4T). This series safe cell-based model, which could be carried out in BSL-2 laboratory, can be used for evaluating NNRTIs candidates.
Full text:
1
Database:
WPRIM
Main subject:
Pharmacology
/
Plasmids
/
Virion
/
Virus Replication
/
Membrane Glycoproteins
/
Transfection
/
Zidovudine
/
Cell Line
/
Viral Envelope Proteins
/
HIV-1
Type of study:
Prognostic_studies
Limits:
Humans
Language:
Zh
Journal:
Acta Pharmaceutica Sinica
Year:
2009
Document type:
Article