In vitro isolation and identification of human immunodeficiency virus (HIV) variants with reduced sensitivity to C-2 symmetrical inhibitors of HIV type 1 protease
| ISSN: | 1091-6490 0027-8424 |
|---|---|
| DOI: | 10.1073/pnas.90.16.7543 |
| Přístupová URL adresa: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::398306193761e402dd34165e7106eb8c https://doi.org/10.1073/pnas.90.16.7543 |
| Rights: | OPEN |
| Přírůstkové číslo: | edsair.doi.dedup.....398306193761e402dd34165e7106eb8c |
| Autor: | Dean L. Winslow, Sena Garber, Caroline Reid, Y. S. E. Cheng, Hodge Carl Nicholas, C. E. Patterson, P. E. Aldrich, Prabhakar K. Jadhav, M. J. Otto |
| Rok vydání: | 1993 |
| Předmět: |
Proteases
medicine.medical_treatment Molecular Sequence Data Biology Virus Cell Line Structure-Activity Relationship HIV Protease Serial passage medicine Humans HIV Protease Inhibitor Amino Acid Sequence Cloning Molecular Codon Virus quantification chemistry.chemical_classification Multidisciplinary Protease Base Sequence Molecular Structure Genetic Variation HIV Protease Inhibitors Virology Molecular biology Recombinant Proteins Enzyme Oligodeoxyribonucleotides chemistry Enzyme inhibitor DNA Viral HIV-1 Mutagenesis Site-Directed biology.protein Research Article |
| Zdroj: | Proceedings of the National Academy of Sciences. 90:7543-7547 |
| ISSN: | 1091-6490 0027-8424 |
| DOI: | 10.1073/pnas.90.16.7543 |
| Popis: | Protease inhibitors are another class of compounds for treatment of human immunodeficiency virus (HIV)-caused disease. The emergence of resistance to the current anti-HIV drugs makes the determination of potential resistance to protease inhibitors imperative. Here we describe the isolation of an HIV type 1 (HIV-1) resistant to an HIV-protease inhibitor. Serial passage of HIV-1 (strain RF) in the presence of the inhibitor, [2-pyridylacetylisoleucylphenylalanyl-psi (CHOH)]2 (P9941), failed to yield a stock of virus with a resistance phenotype. However, variants of the virus with 6- to 8-fold reduced sensitivity to P9941 were selected by using a combination of plaque assay and endpoint titration. Genetic analysis and computer modeling of the variant proteases revealed a single change in the codon for amino acid 82 (Val-->Ala), which resulted in a protease with lower affinity and reduced sensitivity to this inhibitor and certain, but not all, related inhibitors. |
| Databáze: | OpenAIRE |
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