Geographic Distribution of HCV-GT3 Subtypes and Naturally Occurring Resistance Associated Substitutions.
HCV genotype 3 subtypes
NS5A replication complex inhibitors
geographic distribution
natural polymorphisms
resistance-associated substitutions (RASs)
Journal
Viruses
ISSN: 1999-4915
Titre abrégé: Viruses
Pays: Switzerland
ID NLM: 101509722
Informations de publication
Date de publication:
11 02 2019
11 02 2019
Historique:
received:
27
12
2018
accepted:
07
01
2019
entrez:
14
2
2019
pubmed:
14
2
2019
medline:
14
6
2019
Statut:
epublish
Résumé
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. 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. 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 GT3nonA (84.6%) than in GT-3A subtypes (0.8%), and the amino acid change was polymorphic in isolates from Asia. 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.
Sections du résumé
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 GT3nonA (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.
Identifiants
pubmed: 30754682
pii: v11020148
doi: 10.3390/v11020148
pmc: PMC6410151
pii:
doi:
Substances chimiques
Viral Nonstructural Proteins
0
NS-5 protein, hepatitis C virus
EC 2.7.7.48
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Déclaration de conflit d'intérêts
The authors declare no conflict of interest.
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