Establishment of pharmacological evaluation system for non-nucleoside reverse-transcriptase inhibitors resistant HIV-1

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 NNR...

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Bibliographic Details
Published inYao hsüeh hsüeh pao Vol. 44; no. 4; p. 355
Main Authors Cao, Ying-li, Li, Shao-xiong, Chen, Hong, Guo, Ying
Format Journal Article
LanguageChinese
Published China 01.04.2009
Subjects
Anti-HIV Agents - pharmacology
Benzoxazines - pharmacology
Cell Line
Delavirdine - pharmacology
Drug Evaluation, Preclinical - methods
Drug Resistance, Viral
Genetic Vectors
HIV Reverse Transcriptase - antagonists & inhibitors
HIV Reverse Transcriptase - genetics
HIV Reverse Transcriptase - metabolism
HIV-1 - drug effects
HIV-1 - genetics
Humans
Membrane Glycoproteins - genetics
Nevirapine - pharmacology
Plasmids - genetics
Point Mutation
Reverse Transcriptase Inhibitors - pharmacology
Stavudine - pharmacology
Transfection
Viral Envelope Proteins - genetics
Virion - genetics
Virion - metabolism
Virus Replication
Zidovudine - pharmacology
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Summary: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 cel
ISSN:0513-4870