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Geographic Distribution of HCV-GT3 Subtypes and Naturally Occurring Resistance Associated Substitutions

Background: Little is known about the frequency or geographic distributions of naturally occurring resistance-associated substitutions (RASs) in the nonstructural protein 5A (NS5A) domain of hepatitis-C virus (HCV) genotype-3 (GT-3) different subtypes. We investigated naturally occurring GT-3 RASs t...

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Autores principales: Bagaglio, Sabrina, Messina, Emanuela, Hasson, Hamid, Galli, Andrea, Uberti-Foppa, Caterina, Morsica, Giulia
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6410151/
https://www.ncbi.nlm.nih.gov/pubmed/30754682
http://dx.doi.org/10.3390/v11020148
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author Bagaglio, Sabrina
Messina, Emanuela
Hasson, Hamid
Galli, Andrea
Uberti-Foppa, Caterina
Morsica, Giulia
author_facet Bagaglio, Sabrina
Messina, Emanuela
Hasson, Hamid
Galli, Andrea
Uberti-Foppa, Caterina
Morsica, Giulia
author_sort Bagaglio, Sabrina
collection PubMed
description Background: Little is known about the frequency or geographic distributions of naturally occurring resistance-associated substitutions (RASs) in the nonstructural protein 5A (NS5A) domain of hepatitis-C virus (HCV) genotype-3 (GT-3) different subtypes. We investigated naturally occurring GT-3 RASs that confer resistance to NS5A inhibitors. Methods: From a publicly accessible database, we retrieved 58 complete GT-3 genomes and an additional 731 worldwide NS5A sequences from patients infected with GT-3 that were naive to direct-acting antiviral treatment. Results: We performed a phylogenetic analysis of NS5A domains in complete HCV genomes to determine more precisely HCV-GT-3 subtypes, based on commonly used target regions (e.g., 5′untranslated region and NS5B partial domain). Among 789 NS5A sequences, GT-3nonA subtypes were more prevalent in Asia than in other geographic regions (p < 0.0001). The A30K RAS was detected more frequently in HCV GT-3nonA (84.6%) than in GT-3A subtypes (0.8%), and the amino acid change was polymorphic in isolates from Asia. Conclusions: These results provided information on the accuracy of HCV-3 subtyping with a phylogenetic analysis of the NS5A domain with data from the Los Alamos HCV genome database. This information and the worldwide geographic distribution of RASs according to HCV GT-3 subtypes are crucial steps in meeting the challenges of treating HCV GT-3.
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spelling pubmed-64101512019-04-01 Geographic Distribution of HCV-GT3 Subtypes and Naturally Occurring Resistance Associated Substitutions Bagaglio, Sabrina Messina, Emanuela Hasson, Hamid Galli, Andrea Uberti-Foppa, Caterina Morsica, Giulia Viruses Article Background: Little is known about the frequency or geographic distributions of naturally occurring resistance-associated substitutions (RASs) in the nonstructural protein 5A (NS5A) domain of hepatitis-C virus (HCV) genotype-3 (GT-3) different subtypes. We investigated naturally occurring GT-3 RASs that confer resistance to NS5A inhibitors. Methods: From a publicly accessible database, we retrieved 58 complete GT-3 genomes and an additional 731 worldwide NS5A sequences from patients infected with GT-3 that were naive to direct-acting antiviral treatment. Results: We performed a phylogenetic analysis of NS5A domains in complete HCV genomes to determine more precisely HCV-GT-3 subtypes, based on commonly used target regions (e.g., 5′untranslated region and NS5B partial domain). Among 789 NS5A sequences, GT-3nonA subtypes were more prevalent in Asia than in other geographic regions (p < 0.0001). The A30K RAS was detected more frequently in HCV GT-3nonA (84.6%) than in GT-3A subtypes (0.8%), and the amino acid change was polymorphic in isolates from Asia. Conclusions: These results provided information on the accuracy of HCV-3 subtyping with a phylogenetic analysis of the NS5A domain with data from the Los Alamos HCV genome database. This information and the worldwide geographic distribution of RASs according to HCV GT-3 subtypes are crucial steps in meeting the challenges of treating HCV GT-3. MDPI 2019-02-11 /pmc/articles/PMC6410151/ /pubmed/30754682 http://dx.doi.org/10.3390/v11020148 Text en © 2019 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Bagaglio, Sabrina
Messina, Emanuela
Hasson, Hamid
Galli, Andrea
Uberti-Foppa, Caterina
Morsica, Giulia
Geographic Distribution of HCV-GT3 Subtypes and Naturally Occurring Resistance Associated Substitutions
title Geographic Distribution of HCV-GT3 Subtypes and Naturally Occurring Resistance Associated Substitutions
title_full Geographic Distribution of HCV-GT3 Subtypes and Naturally Occurring Resistance Associated Substitutions
title_fullStr Geographic Distribution of HCV-GT3 Subtypes and Naturally Occurring Resistance Associated Substitutions
title_full_unstemmed Geographic Distribution of HCV-GT3 Subtypes and Naturally Occurring Resistance Associated Substitutions
title_short Geographic Distribution of HCV-GT3 Subtypes and Naturally Occurring Resistance Associated Substitutions
title_sort geographic distribution of hcv-gt3 subtypes and naturally occurring resistance associated substitutions
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6410151/
https://www.ncbi.nlm.nih.gov/pubmed/30754682
http://dx.doi.org/10.3390/v11020148
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