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 |
Appears in Collections: | (CAB) Artículos |
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