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Factors Influencing the Prevalence of Resistance-Associated Substitutions in NS5A Protein in Treatment-Naive Patients with Chronic Hepatitis C
Direct-acting antivirals (DAAs) revolutionized treatment of hepatitis C virus (HCV) infection. Resistance-associated substitutions (RASs) present at the baseline impair response to DAA due to rapid selection of resistant HCV strains. NS5A is indispensable target of the current DAA treatment regimens...
Autores principales: | , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2020
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7235841/ https://www.ncbi.nlm.nih.gov/pubmed/32272736 http://dx.doi.org/10.3390/biomedicines8040080 |
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author | Kyuregyan, Karen K. Kichatova, Vera S. Karlsen, Anastasiya A. Isaeva, Olga V. Solonin, Sergei A. Petkov, Stefan Nielsen, Morten Isaguliants, Maria G. Mikhailov, Mikhail I. |
author_facet | Kyuregyan, Karen K. Kichatova, Vera S. Karlsen, Anastasiya A. Isaeva, Olga V. Solonin, Sergei A. Petkov, Stefan Nielsen, Morten Isaguliants, Maria G. Mikhailov, Mikhail I. |
author_sort | Kyuregyan, Karen K. |
collection | PubMed |
description | Direct-acting antivirals (DAAs) revolutionized treatment of hepatitis C virus (HCV) infection. Resistance-associated substitutions (RASs) present at the baseline impair response to DAA due to rapid selection of resistant HCV strains. NS5A is indispensable target of the current DAA treatment regimens. We evaluated prevalence of RASs in NS5A in DAA-naïve patients infected with HCV 1a (n = 19), 1b (n = 93), and 3a (n = 90) before systematic DAA application in the territory of the Russian Federation. Total proportion of strains carrying at least one RAS constituted 35.1% (71/202). In HCV 1a we detected only M28V (57.9%) attributed to a founder effect. Common RASs in HCV 1b were R30Q (7.5%), L31M (5.4%), P58S (4.4%), and Y93H (5.4%); in HCV 3a, A30S (31.0%), A30K (5.7%), S62L (8.9%), and Y93H (2.2%). Prevalence of RASs in NS5A of HCV 1b and 3a was similar to that worldwide, including countries practicing massive DAA application, i.e., it was not related to treatment. NS5A with and without RASs exhibited different co-variance networks, which could be attributed to the necessity to preserve viral fitness. Majority of RASs were localized in polymorphic regions subjected to immune pressure, with selected substitutions allowing immune escape. Altogether, this explains high prevalence of RAS in NS5A and low barrier for their appearance in DAA-inexperienced population. |
format | Online Article Text |
id | pubmed-7235841 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-72358412020-05-22 Factors Influencing the Prevalence of Resistance-Associated Substitutions in NS5A Protein in Treatment-Naive Patients with Chronic Hepatitis C Kyuregyan, Karen K. Kichatova, Vera S. Karlsen, Anastasiya A. Isaeva, Olga V. Solonin, Sergei A. Petkov, Stefan Nielsen, Morten Isaguliants, Maria G. Mikhailov, Mikhail I. Biomedicines Article Direct-acting antivirals (DAAs) revolutionized treatment of hepatitis C virus (HCV) infection. Resistance-associated substitutions (RASs) present at the baseline impair response to DAA due to rapid selection of resistant HCV strains. NS5A is indispensable target of the current DAA treatment regimens. We evaluated prevalence of RASs in NS5A in DAA-naïve patients infected with HCV 1a (n = 19), 1b (n = 93), and 3a (n = 90) before systematic DAA application in the territory of the Russian Federation. Total proportion of strains carrying at least one RAS constituted 35.1% (71/202). In HCV 1a we detected only M28V (57.9%) attributed to a founder effect. Common RASs in HCV 1b were R30Q (7.5%), L31M (5.4%), P58S (4.4%), and Y93H (5.4%); in HCV 3a, A30S (31.0%), A30K (5.7%), S62L (8.9%), and Y93H (2.2%). Prevalence of RASs in NS5A of HCV 1b and 3a was similar to that worldwide, including countries practicing massive DAA application, i.e., it was not related to treatment. NS5A with and without RASs exhibited different co-variance networks, which could be attributed to the necessity to preserve viral fitness. Majority of RASs were localized in polymorphic regions subjected to immune pressure, with selected substitutions allowing immune escape. Altogether, this explains high prevalence of RAS in NS5A and low barrier for their appearance in DAA-inexperienced population. MDPI 2020-04-07 /pmc/articles/PMC7235841/ /pubmed/32272736 http://dx.doi.org/10.3390/biomedicines8040080 Text en © 2020 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 Kyuregyan, Karen K. Kichatova, Vera S. Karlsen, Anastasiya A. Isaeva, Olga V. Solonin, Sergei A. Petkov, Stefan Nielsen, Morten Isaguliants, Maria G. Mikhailov, Mikhail I. Factors Influencing the Prevalence of Resistance-Associated Substitutions in NS5A Protein in Treatment-Naive Patients with Chronic Hepatitis C |
title | Factors Influencing the Prevalence of Resistance-Associated Substitutions in NS5A Protein in Treatment-Naive Patients with Chronic Hepatitis C |
title_full | Factors Influencing the Prevalence of Resistance-Associated Substitutions in NS5A Protein in Treatment-Naive Patients with Chronic Hepatitis C |
title_fullStr | Factors Influencing the Prevalence of Resistance-Associated Substitutions in NS5A Protein in Treatment-Naive Patients with Chronic Hepatitis C |
title_full_unstemmed | Factors Influencing the Prevalence of Resistance-Associated Substitutions in NS5A Protein in Treatment-Naive Patients with Chronic Hepatitis C |
title_short | Factors Influencing the Prevalence of Resistance-Associated Substitutions in NS5A Protein in Treatment-Naive Patients with Chronic Hepatitis C |
title_sort | factors influencing the prevalence of resistance-associated substitutions in ns5a protein in treatment-naive patients with chronic hepatitis c |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7235841/ https://www.ncbi.nlm.nih.gov/pubmed/32272736 http://dx.doi.org/10.3390/biomedicines8040080 |
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