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Molecular genotypes of gag sequences in HIV-1 infected children treated with antiretroviral therapy in Vietnam

BACKGROUND: Gag protein of human immunodeficiency virus (HIV) has been reported to play a crucial role in establishing infection, viral replication, and disease progression; thus, gag might be related to treatment response. The objective of this study was to investigate molecular genotypes of the ga...

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Autores principales: Dang, Linh Vu Phuong, Pham, Hung Viet, Dinh, Thanh Thi, Vu, Phuong Thi, Nguyen, Lam Van, Le, Hai Thanh, Larsson, Mattias, Olson, Linus
Formato: Online Artículo Texto
Lenguaje:English
Publicado: SAGE Publications 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7502858/
https://www.ncbi.nlm.nih.gov/pubmed/32994994
http://dx.doi.org/10.1177/2049936120958536
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author Dang, Linh Vu Phuong
Pham, Hung Viet
Dinh, Thanh Thi
Vu, Phuong Thi
Nguyen, Lam Van
Le, Hai Thanh
Larsson, Mattias
Olson, Linus
author_facet Dang, Linh Vu Phuong
Pham, Hung Viet
Dinh, Thanh Thi
Vu, Phuong Thi
Nguyen, Lam Van
Le, Hai Thanh
Larsson, Mattias
Olson, Linus
author_sort Dang, Linh Vu Phuong
collection PubMed
description BACKGROUND: Gag protein of human immunodeficiency virus (HIV) has been reported to play a crucial role in establishing infection, viral replication, and disease progression; thus, gag might be related to treatment response. The objective of this study was to investigate molecular genotypes of the gag gene, particularly the important functional binding domains in relation to treatment outcomes. METHODS: HIV-infected children enrolled and treated at Vietnam National Children’s Hospital were recruited in the study. A total of 25 gag sequences were generated and used to construct phylogenetic trees and aligned with a reference sequence comparing 17 functional domains. RESULTS: We found that all patients in a treatment failure (TF) group belonged to one cluster of the phylogenetic tree. In addition, the rate of mutations was significantly higher in TF compared with a treatment success (TS) group, specifically the PIP2 recognition motif, and the nucleocapsid basic and zinc motif 2 domains [median and (interquartile range (IQR): 12.5 (6.25–12.5) versus 50 (25–50), p < 0.01; 0 (0–0) versus 0 (0–21.43), p = 0.03 and 0 (0–7.14) versus 7.14 (7.14–7.14), p = 0.04, respectively]. When analyzing gag sequences at different time points in seven patients, we did not observe a consistent mutation pattern related to treatment response. CONCLUSION: Gag mutations in certain domains might be associated with increased viral load; therefore, studying the molecular genotype of the gag gene might be beneficial in monitoring treatment response in HIV-infected children.
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spelling pubmed-75028582020-09-28 Molecular genotypes of gag sequences in HIV-1 infected children treated with antiretroviral therapy in Vietnam Dang, Linh Vu Phuong Pham, Hung Viet Dinh, Thanh Thi Vu, Phuong Thi Nguyen, Lam Van Le, Hai Thanh Larsson, Mattias Olson, Linus Ther Adv Infect Dis Original Research BACKGROUND: Gag protein of human immunodeficiency virus (HIV) has been reported to play a crucial role in establishing infection, viral replication, and disease progression; thus, gag might be related to treatment response. The objective of this study was to investigate molecular genotypes of the gag gene, particularly the important functional binding domains in relation to treatment outcomes. METHODS: HIV-infected children enrolled and treated at Vietnam National Children’s Hospital were recruited in the study. A total of 25 gag sequences were generated and used to construct phylogenetic trees and aligned with a reference sequence comparing 17 functional domains. RESULTS: We found that all patients in a treatment failure (TF) group belonged to one cluster of the phylogenetic tree. In addition, the rate of mutations was significantly higher in TF compared with a treatment success (TS) group, specifically the PIP2 recognition motif, and the nucleocapsid basic and zinc motif 2 domains [median and (interquartile range (IQR): 12.5 (6.25–12.5) versus 50 (25–50), p < 0.01; 0 (0–0) versus 0 (0–21.43), p = 0.03 and 0 (0–7.14) versus 7.14 (7.14–7.14), p = 0.04, respectively]. When analyzing gag sequences at different time points in seven patients, we did not observe a consistent mutation pattern related to treatment response. CONCLUSION: Gag mutations in certain domains might be associated with increased viral load; therefore, studying the molecular genotype of the gag gene might be beneficial in monitoring treatment response in HIV-infected children. SAGE Publications 2020-09-17 /pmc/articles/PMC7502858/ /pubmed/32994994 http://dx.doi.org/10.1177/2049936120958536 Text en © The Author(s), 2020 https://creativecommons.org/licenses/by-nc/4.0/ This article is distributed under the terms of the Creative Commons Attribution-NonCommercial 4.0 License (https://creativecommons.org/licenses/by-nc/4.0/) which permits non-commercial use, reproduction and distribution of the work without further permission provided the original work is attributed as specified on the SAGE and Open Access page (https://us.sagepub.com/en-us/nam/open-access-at-sage).
spellingShingle Original Research
Dang, Linh Vu Phuong
Pham, Hung Viet
Dinh, Thanh Thi
Vu, Phuong Thi
Nguyen, Lam Van
Le, Hai Thanh
Larsson, Mattias
Olson, Linus
Molecular genotypes of gag sequences in HIV-1 infected children treated with antiretroviral therapy in Vietnam
title Molecular genotypes of gag sequences in HIV-1 infected children treated with antiretroviral therapy in Vietnam
title_full Molecular genotypes of gag sequences in HIV-1 infected children treated with antiretroviral therapy in Vietnam
title_fullStr Molecular genotypes of gag sequences in HIV-1 infected children treated with antiretroviral therapy in Vietnam
title_full_unstemmed Molecular genotypes of gag sequences in HIV-1 infected children treated with antiretroviral therapy in Vietnam
title_short Molecular genotypes of gag sequences in HIV-1 infected children treated with antiretroviral therapy in Vietnam
title_sort molecular genotypes of gag sequences in hiv-1 infected children treated with antiretroviral therapy in vietnam
topic Original Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7502858/
https://www.ncbi.nlm.nih.gov/pubmed/32994994
http://dx.doi.org/10.1177/2049936120958536
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