Please use this identifier to cite or link to this item: http://hdl.handle.net/20.500.12666/108
Title: Amino acid substitutions associated with treatment failure for Hepatitis C virus infection
Authors: Soria, María Eugenia
García Crespo, Carlos
Martínez González, Brenda
Vázquez Sirvent, L.
Lobo Vega, Rebeca
Ávila, Ana Isabel de
Gallego, Isabel
Chen, Qian
García Cehic, Damir
Llorens Revull, Meritxell
Briones, C.
Gómez, Jordi
Ferrer Orta, Cristina
Verdaguer, Nuria
Gregori, Josep
Rodríguez Frías, Francisco
Buti, María
Ignacio Esteban, Juan
Domingo, Esteban
Quer, Josep
Perales, Celia
Keywords: Next-generation sequencing;Viral quasispecies;Viral fitness;Antiviral Agents;Viral diagnostics;Treatment planning
Issue Date: Dec-2020
Publisher: American Society for Microbiology
DOI: 10.1128/JCM.01985-20
Published version: https://jcm.asm.org/content/58/12/e01985-20
Citation: Journal of Clinical Microbiology 58(12): e01985-20 (2020)
Abstract: 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.
URI: http://hdl.handle.net/20.500.12666/108
E-ISSN: 1098-660X
ISSN: 0095-1137
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