Amino Acid Substitutions Associated with Treatment Failure for Hepatitis C Virus Infection.
antiviral agents
next-generation sequencing
treatment planning
viral diagnostics
viral fitness
viral quasispecies
Journal
Journal of clinical microbiology
ISSN: 1098-660X
Titre abrégé: J Clin Microbiol
Pays: United States
ID NLM: 7505564
Informations de publication
Date de publication:
18 11 2020
18 11 2020
Historique:
received:
28
07
2020
accepted:
21
09
2020
pubmed:
2
10
2020
medline:
24
6
2021
entrez:
1
10
2020
Statut:
epublish
Résumé
Despite the high virological response rates achieved with current directly acting antiviral agents (DAAs) against hepatitis C virus (HCV), around 2% to 5% of treated patients do not achieve a sustained viral response. The identification of amino acid substitutions associated with treatment failure requires analytical designs, such as subtype-specific ultradeep sequencing (UDS) methods, for HCV characterization and patient management. Using this procedure, we have identified six highly represented amino acid substitutions (HRSs) in NS5A and NS5B of HCV, which are not bona fide resistance-associated substitutions (RAS), from 220 patients who failed therapy. They were present frequently in basal and posttreatment virus of patients who failed different DAA-based therapies. Contrary to several RAS, HRSs belong to the acceptable subset of substitutions according to the PAM250 replacement matrix. Their mutant frequency, measured by the number of deep sequencing reads within the HCV quasispecies that encode the relevant substitutions, ranged between 90% and 100% in most cases. They also have limited predicted disruptive effects on the three-dimensional structures of the proteins harboring them. Possible mechanisms of HRS origin and dominance, as well as their potential predictive value for treatment response, are discussed.
Identifiants
pubmed: 32999010
pii: JCM.01985-20
doi: 10.1128/JCM.01985-20
pmc: PMC7685896
pii:
doi:
Substances chimiques
Antiviral Agents
0
Viral Nonstructural Proteins
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Informations de copyright
Copyright © 2020 American Society for Microbiology.
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