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Natural polymorphisms and unusual mutations in HIV-1 protease with potential antiretroviral resistance: a bioinformatic analysis
BACKGROUND: The correlations of genotypic and phenotypic tests with treatment, clinical history and the significance of mutations in viruses of HIV-infected patients are used to establish resistance mutations to protease inhibitors (PIs). Emerging mutations in human immunodeficiency virus type 1 (HI...
Autores principales: | , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
BioMed Central
2014
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4003850/ https://www.ncbi.nlm.nih.gov/pubmed/24629078 http://dx.doi.org/10.1186/1471-2105-15-72 |
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author | Mata-Munguía, Carlos Escoto-Delgadillo, Martha Torres-Mendoza, Blanca Flores-Soto, Mario Vázquez-Torres, Mildred Gálvez-Gastelum, Francisco Viniegra-Osorio, Arturo Castillero-Manzano, Marcelo Vázquez-Valls, Eduardo |
author_facet | Mata-Munguía, Carlos Escoto-Delgadillo, Martha Torres-Mendoza, Blanca Flores-Soto, Mario Vázquez-Torres, Mildred Gálvez-Gastelum, Francisco Viniegra-Osorio, Arturo Castillero-Manzano, Marcelo Vázquez-Valls, Eduardo |
author_sort | Mata-Munguía, Carlos |
collection | PubMed |
description | BACKGROUND: The correlations of genotypic and phenotypic tests with treatment, clinical history and the significance of mutations in viruses of HIV-infected patients are used to establish resistance mutations to protease inhibitors (PIs). Emerging mutations in human immunodeficiency virus type 1 (HIV-1) protease confer resistance to PIs by inducing structural changes at the ligand interaction site. The aim of this study was to establish an in silico structural relationship between natural HIV-1 polymorphisms and unusual HIV-1 mutations that confer resistance to PIs. RESULTS: Protease sequences isolated from 151 Mexican HIV-1 patients that were naïve to, or subjected to antiretroviral therapy, were examined. We identified 41 unrelated resistance mutations with a prevalence greater than 1%. Among these mutations, nine exhibited positive selection, three were natural polymorphisms (L63S/V/H) in a codon associated with drug resistance, and six were unusual mutations (L5F, D29V, L63R/G, P79L and T91V). The D29V mutation, with a prevalence of 1.32% in the studied population, was only found in patients treated with antiretroviral drugs. Using in silico modelling, we observed that D29V formed unstable protease complexes when were docked with lopinavir, saquinavir, darunavir, tipranavir, indinavir and atazanavir. CONCLUSIONS: The structural correlation of natural polymorphisms and unusual mutations with drug resistance is useful for the identification of HIV-1 variants with potential resistance to PIs. The D29V mutation likely confers a selection advantage in viruses; however, in silico, presence of this mutation results in unstable enzyme/PI complexes, that possibly induce resistance to PIs. |
format | Online Article Text |
id | pubmed-4003850 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2014 |
publisher | BioMed Central |
record_format | MEDLINE/PubMed |
spelling | pubmed-40038502014-04-30 Natural polymorphisms and unusual mutations in HIV-1 protease with potential antiretroviral resistance: a bioinformatic analysis Mata-Munguía, Carlos Escoto-Delgadillo, Martha Torres-Mendoza, Blanca Flores-Soto, Mario Vázquez-Torres, Mildred Gálvez-Gastelum, Francisco Viniegra-Osorio, Arturo Castillero-Manzano, Marcelo Vázquez-Valls, Eduardo BMC Bioinformatics Research Article BACKGROUND: The correlations of genotypic and phenotypic tests with treatment, clinical history and the significance of mutations in viruses of HIV-infected patients are used to establish resistance mutations to protease inhibitors (PIs). Emerging mutations in human immunodeficiency virus type 1 (HIV-1) protease confer resistance to PIs by inducing structural changes at the ligand interaction site. The aim of this study was to establish an in silico structural relationship between natural HIV-1 polymorphisms and unusual HIV-1 mutations that confer resistance to PIs. RESULTS: Protease sequences isolated from 151 Mexican HIV-1 patients that were naïve to, or subjected to antiretroviral therapy, were examined. We identified 41 unrelated resistance mutations with a prevalence greater than 1%. Among these mutations, nine exhibited positive selection, three were natural polymorphisms (L63S/V/H) in a codon associated with drug resistance, and six were unusual mutations (L5F, D29V, L63R/G, P79L and T91V). The D29V mutation, with a prevalence of 1.32% in the studied population, was only found in patients treated with antiretroviral drugs. Using in silico modelling, we observed that D29V formed unstable protease complexes when were docked with lopinavir, saquinavir, darunavir, tipranavir, indinavir and atazanavir. CONCLUSIONS: The structural correlation of natural polymorphisms and unusual mutations with drug resistance is useful for the identification of HIV-1 variants with potential resistance to PIs. The D29V mutation likely confers a selection advantage in viruses; however, in silico, presence of this mutation results in unstable enzyme/PI complexes, that possibly induce resistance to PIs. BioMed Central 2014-03-15 /pmc/articles/PMC4003850/ /pubmed/24629078 http://dx.doi.org/10.1186/1471-2105-15-72 Text en Copyright © 2014 Mata-Munguía et al.; licensee BioMed Central Ltd. http://creativecommons.org/licenses/by/2.0 This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited. |
spellingShingle | Research Article Mata-Munguía, Carlos Escoto-Delgadillo, Martha Torres-Mendoza, Blanca Flores-Soto, Mario Vázquez-Torres, Mildred Gálvez-Gastelum, Francisco Viniegra-Osorio, Arturo Castillero-Manzano, Marcelo Vázquez-Valls, Eduardo Natural polymorphisms and unusual mutations in HIV-1 protease with potential antiretroviral resistance: a bioinformatic analysis |
title | Natural polymorphisms and unusual mutations in HIV-1 protease with potential antiretroviral resistance: a bioinformatic analysis |
title_full | Natural polymorphisms and unusual mutations in HIV-1 protease with potential antiretroviral resistance: a bioinformatic analysis |
title_fullStr | Natural polymorphisms and unusual mutations in HIV-1 protease with potential antiretroviral resistance: a bioinformatic analysis |
title_full_unstemmed | Natural polymorphisms and unusual mutations in HIV-1 protease with potential antiretroviral resistance: a bioinformatic analysis |
title_short | Natural polymorphisms and unusual mutations in HIV-1 protease with potential antiretroviral resistance: a bioinformatic analysis |
title_sort | natural polymorphisms and unusual mutations in hiv-1 protease with potential antiretroviral resistance: a bioinformatic analysis |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4003850/ https://www.ncbi.nlm.nih.gov/pubmed/24629078 http://dx.doi.org/10.1186/1471-2105-15-72 |
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