ArticleAntimicrobial agents and chemotherapy2005
Atazanavir signature I50L resistance substitution accounts for unique phenotype of increased susceptibility to other protease inhibitors in a variety of human immunodeficiency virus type 1 genetic backbones.
Article in Antimicrobial agents and chemotherapy, 2005. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
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Who cites it
15 citing papers in PubMed, 37 citations in OpenAlex.
- Comprehending the Structure, Dynamics, and Mechanism of Action of Drug-Resistant HIV Protease.ACS omega · 2023Review
- Non-active site mutants of HIV-1 protease influence resistance and sensitisation towards protease inhibitors.Retrovirology · 2020Article
- HIV-1 Drug Resistance Mutations: Potential Applications for Point-of-Care Genotypic Resistance Testing.PloS one · 2015Article
- Collinearity of protease mutations in HIV-1 samples with high-level protease inhibitor class resistance.The Journal of antimicrobial chemotherapy · 2013Article
- Mutations in multiple domains of Gag drive the emergence of in vitro resistance to the phosphonate-containing HIV-1 protease inhibitor GS-8374.Journal of virology · 2013Article
- Effect of natural polymorphisms in the HIV-1 CRF02_AG protease on protease inhibitor hypersusceptibility.Antimicrobial agents and chemotherapy · 2012Article
- Interaction of I50V mutant and I50L/A71V double mutant HIV-protease with inhibitor TMC114 (darunavir): molecular dynamics simulation and binding free energy studies.The journal of physical chemistry. B · 2012Article
- A multifaceted analysis of HIV-1 protease multidrug resistance phenotypes.BMC bioinformatics · 2011Article
- Distinct functions of NS5A in hepatitis C virus RNA replication uncovered by studies with the NS5A inhibitor BMS-790052.Journal of virology · 2011Article
- Atazanavir/ritonavir-based combination antiretroviral therapy for treatment of HIV-1 infection in adults.Future virology · 2011Article
- HIV-1 protease mutations and protease inhibitor cross-resistance.Antimicrobial agents and chemotherapy · 2010Article
- Review
- Review
- Review
- X-ray crystal structures of human immunodeficiency virus type 1 protease mutants complexed with atazanavir.Journal of virology · 2007Article
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Authors and funding
5 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Substitution of leucine for isoleucine at residue 50 (I50L) of human immunodeficiency virus (HIV) protease is the signature substitution for atazanavir (ATV) resistance. A unique phenotypic profile has been associated with viruses containing the I50L substitution, which produces ATV-specific resistance and increased susceptibility to most other approved HIV protease inhibitors (PIs). The basis for this unique phenotype has not been clearly elucidated. In this report, a direct effect of I50L on the susceptibility to the PI class is described. Cell-based protease assays using wild-type and PI-resistant proteases from laboratory and clinical isolates and in vitro antiviral assays were used to demonstrate a strong concordance between changes in PI susceptibility at the level of protease inhibition and changes in susceptibility observed at the level of virus infection. The results show that the induction of ATV resistance and increased susceptibility to other PIs by the I50L substitution is likely determined at the level of protease inhibition. Moreover, the I50L substitution functions to increase PI susceptibility even in the presence of other primary and secondary PI resistance substitutions. These findings may have implications regarding the optimal sequencing of PI therapies necessary to preserve PI treatment options of patients with ATV-resistant HIV infections.
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