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• W2012153386 endingPage "5098" @default.
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• W2012153386 abstract "Emergence of drug-resistant mutant viruses during the course of antiretroviral therapy is a major hurdle that limits the success of chemotherapeutic treatment to suppress human immunodeficiency virus type 1 (HIV-1) replication and AIDS progression. Development of new drugs and careful patient management based on resistance genotyping data are important for enhancing therapeutic efficacy. However, identifying changes leading to drug resistance can take years of clinical studies, and conventional in vitro assays are limited in generating reliable drug resistance data. Here we present an efficient in vitro screening assay for selecting drug-resistant variants from a library of randomly mutated HIV-1 strains generated by transposon-directed base-exchange mutagenesis. As a test of principle, we screened a library of mutant HIV-1 strains containing random mutations in the protease gene by using a reporter T-cell line in the presence of the protease inhibitor (PI) nelfinavir (NFV). Analysis of replicating viruses from a single round of infection identified 50 amino acid substitutions at 35 HIV-1 protease residue positions. The selected mutant viruses showed specific resistance to NFV and included most of the known NFV resistance mutations. Therefore, the new assay is efficient for identifying changes leading to drug resistance. The data also provide insights into the molecular mechanisms underlying the development of drug resistance." @default.
• W2012153386 created "2016-06-24" @default.
• W2012153386 creator A5003663681 @default.
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• W2012153386 date "2011-08-29" @default.
• W2012153386 modified "2023-09-24" @default.
• W2012153386 title "Efficient Identification of Human Immunodeficiency Virus Type 1 Mutants Resistant to a Protease Inhibitor by Using a Random Mutant Library" @default.
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• W2012153386 doi "https://doi.org/10.1128/aac.00687-11" @default.
• W2012153386 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/3195011" @default.
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• W2012153386 hasPublicationYear "2011" @default.
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