title: [Establishment of pharmacological evaluation system for non-nucleoside reverse-transcriptase inhibitors resistant HIV-1].
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.
authors: Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100050, China.
authors: Ying-li
authors: YL
authors: Cao
authors: Shao-xiong
authors: SX
authors: Li
authors: Hong
authors: H
authors: Chen
authors: Ying
authors: Y
authors: Guo
mesh_terms: D000480:Alkynes; D019380:Anti-HIV Agents / Q000494:pharmacology*; D048588:Benzoxazines / Q000494:pharmacology; D002460:Cell Line; D003521:Cyclopropanes; D020008:Delavirdine / Q000494:pharmacology; D004353:Drug Evaluation, Preclinical / Q000379:methods*; D024882:Drug Resistance, Viral; D005822:Genetic Vectors; D054303:HIV Reverse Transcriptase / Q000037:antagonists & inhibitors / Q000235:genetics* / Q000378:metabolism; D015497:HIV-1 / Q000187:drug effects* / Q000235:genetics; D006801:Humans; D008562:Membrane Glycoproteins / Q000235:genetics; D019829:Nevirapine / Q000494:pharmacology; D010957:Plasmids / Q000235:genetics; D017354:Point Mutation; D018894:Reverse Transcriptase Inhibitors / Q000494:pharmacology*; D018119:Stavudine / Q000494:pharmacology; D014162:Transfection; D014759:Viral Envelope Proteins / Q000235:genetics; D014771:Virion / Q000235:genetics / Q000378:metabolism; D014779:Virus Replication; D015215:Zidovudine / Q000494:pharmacology
chemical_list: D000480:Alkynes; D019380:Anti-HIV Agents; D048588:Benzoxazines; D003521:Cyclopropanes; C028391:G protein, vesicular stomatitis virus; D008562:Membrane Glycoproteins; D018894:Reverse Transcriptase Inhibitors; D014759:Viral Envelope Proteins; D015215:Zidovudine; D019829:Nevirapine; D018119:Stavudine; D020008:Delavirdine; D054303:HIV Reverse Transcriptase; C098320:efavirenz