Factors influencing the prevalence of resistance-associated substitutions in NS5A protein in treatment-naive patients with chronic hepatitis C

Autores
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.
Año de publicación
2020
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
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.
Fil: Kyuregyan, Karen K.. Russian Academy Of Sciences; Rusia. Russian Medical Academy Of Continuous Professional Education; Rusia. I. I. Mechnikov Research Institute For Vaccines And Sera; Rusia
Fil: Kichatova, Vera S.. Russian Medical Academy Of Continuous Professional Education; Rusia. Russian Academy Of Sciences; Rusia. I. I. Mechnikov Research Institute For Vaccines And Sera; Rusia
Fil: Karlsen, Anastasiya A.. I. I. Mechnikov Research Institute For Vaccines And Sera; Rusia. Russian Medical Academy Of Continuous Professional Education; Rusia. Russian Academy Of Sciences; Rusia
Fil: Isaeva, Olga V.. I. I. Mechnikov Research Institute For Vaccines And Sera; Rusia. Russian Medical Academy Of Continuous Professional Education; Rusia
Fil: Solonin, Sergei A.. N.V. Sklifosovsky Research Institute for Emergency Medicine; Rusia
Fil: Petkov, Stefan. Karolinska Huddinge Hospital. Karolinska Institutet; Suecia
Fil: Nielsen, Morten. Technical University of Denmark; Dinamarca. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto de Investigaciones Biotecnológicas. Universidad Nacional de San Martín. Instituto de Investigaciones Biotecnológicas; Argentina
Fil: Isaguliants, Maria G.. Russian Academy Of Sciences; Rusia. Karolinska Huddinge Hospital. Karolinska Institutet; Suecia
Fil: Mikhailov, Mikhail I.. Russian Medical Academy Of Continuous Professional Education; Rusia. I. I. Mechnikov Research Institute For Vaccines And Sera; Rusia
Materia
AMINO ACID COVARIANCE
DIRECT-ACTING ANTIVIRALS
HEPATITIS C VIRUS (HCV)
IMMUNE ESCAPE
NS5A
RESISTANCE-ASSOCIATED SUBSTITUTIONS
Nivel de accesibilidad
acceso abierto
Condiciones de uso
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
Repositorio
CONICET Digital (CONICET)
Institución
Consejo Nacional de Investigaciones Científicas y Técnicas
OAI Identificador
oai:ri.conicet.gov.ar:11336/112669
Acceder
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oai_identifier_str oai:ri.conicet.gov.ar:11336/112669
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling Factors influencing the prevalence of resistance-associated substitutions in NS5A protein in treatment-naive patients with chronic hepatitis CKyuregyan, Karen K.Kichatova, Vera S.Karlsen, Anastasiya A.Isaeva, Olga V.Solonin, Sergei A.Petkov, StefanNielsen, MortenIsaguliants, Maria G.Mikhailov, Mikhail I.AMINO ACID COVARIANCEDIRECT-ACTING ANTIVIRALSHEPATITIS C VIRUS (HCV)IMMUNE ESCAPENS5ARESISTANCE-ASSOCIATED SUBSTITUTIONShttps://purl.org/becyt/ford/3.3https://purl.org/becyt/ford/3Direct-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.Fil: Kyuregyan, Karen K.. Russian Academy Of Sciences; Rusia. Russian Medical Academy Of Continuous Professional Education; Rusia. I. I. Mechnikov Research Institute For Vaccines And Sera; RusiaFil: Kichatova, Vera S.. Russian Medical Academy Of Continuous Professional Education; Rusia. Russian Academy Of Sciences; Rusia. I. I. Mechnikov Research Institute For Vaccines And Sera; RusiaFil: Karlsen, Anastasiya A.. I. I. Mechnikov Research Institute For Vaccines And Sera; Rusia. Russian Medical Academy Of Continuous Professional Education; Rusia. Russian Academy Of Sciences; RusiaFil: Isaeva, Olga V.. I. I. Mechnikov Research Institute For Vaccines And Sera; Rusia. Russian Medical Academy Of Continuous Professional Education; RusiaFil: Solonin, Sergei A.. N.V. Sklifosovsky Research Institute for Emergency Medicine; RusiaFil: Petkov, Stefan. Karolinska Huddinge Hospital. Karolinska Institutet; SueciaFil: Nielsen, Morten. Technical University of Denmark; Dinamarca. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto de Investigaciones Biotecnológicas. Universidad Nacional de San Martín. Instituto de Investigaciones Biotecnológicas; ArgentinaFil: Isaguliants, Maria G.. Russian Academy Of Sciences; Rusia. Karolinska Huddinge Hospital. Karolinska Institutet; SueciaFil: Mikhailov, Mikhail I.. Russian Medical Academy Of Continuous Professional Education; Rusia. I. I. Mechnikov Research Institute For Vaccines And Sera; RusiaMDPI2020-04info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/112669Kyuregyan, Karen K.; Kichatova, Vera S.; Karlsen, Anastasiya A.; Isaeva, Olga V.; Solonin, Sergei A.; et al.; Factors influencing the prevalence of resistance-associated substitutions in NS5A protein in treatment-naive patients with chronic hepatitis C; MDPI; Biomedicines; 8; 4; 4-2020; 1-202227-9059CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/url/https://www.mdpi.com/2227-9059/8/4/80info:eu-repo/semantics/altIdentifier/doi/10.3390/biomedicines8040080info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-03T09:57:13Zoai:ri.conicet.gov.ar:11336/112669instacron:CONICETInstitucionalhttp://ri.conicet.gov.ar/Organismo científico-tecnológicoNo correspondehttp://ri.conicet.gov.ar/oai/requestdasensio@conicet.gov.ar; lcarlino@conicet.gov.arArgentinaNo correspondeNo correspondeNo correspondeopendoar:34982025-09-03 09:57:13.775CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv 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
spellingShingle Factors influencing the prevalence of resistance-associated substitutions in NS5A protein in treatment-naive patients with chronic hepatitis C
Kyuregyan, Karen K.
AMINO ACID COVARIANCE
DIRECT-ACTING ANTIVIRALS
HEPATITIS C VIRUS (HCV)
IMMUNE ESCAPE
NS5A
RESISTANCE-ASSOCIATED SUBSTITUTIONS
title_short 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_sort Factors influencing the prevalence of resistance-associated substitutions in NS5A protein in treatment-naive patients with chronic hepatitis C
dc.creator.none.fl_str_mv 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 Kyuregyan, Karen K.
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_role author
author2 Kichatova, Vera S.
Karlsen, Anastasiya A.
Isaeva, Olga V.
Solonin, Sergei A.
Petkov, Stefan
Nielsen, Morten
Isaguliants, Maria G.
Mikhailov, Mikhail I.
author2_role author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv AMINO ACID COVARIANCE
DIRECT-ACTING ANTIVIRALS
HEPATITIS C VIRUS (HCV)
IMMUNE ESCAPE
NS5A
RESISTANCE-ASSOCIATED SUBSTITUTIONS
topic AMINO ACID COVARIANCE
DIRECT-ACTING ANTIVIRALS
HEPATITIS C VIRUS (HCV)
IMMUNE ESCAPE
NS5A
RESISTANCE-ASSOCIATED SUBSTITUTIONS
purl_subject.fl_str_mv https://purl.org/becyt/ford/3.3
https://purl.org/becyt/ford/3
dc.description.none.fl_txt_mv 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.
Fil: Kyuregyan, Karen K.. Russian Academy Of Sciences; Rusia. Russian Medical Academy Of Continuous Professional Education; Rusia. I. I. Mechnikov Research Institute For Vaccines And Sera; Rusia
Fil: Kichatova, Vera S.. Russian Medical Academy Of Continuous Professional Education; Rusia. Russian Academy Of Sciences; Rusia. I. I. Mechnikov Research Institute For Vaccines And Sera; Rusia
Fil: Karlsen, Anastasiya A.. I. I. Mechnikov Research Institute For Vaccines And Sera; Rusia. Russian Medical Academy Of Continuous Professional Education; Rusia. Russian Academy Of Sciences; Rusia
Fil: Isaeva, Olga V.. I. I. Mechnikov Research Institute For Vaccines And Sera; Rusia. Russian Medical Academy Of Continuous Professional Education; Rusia
Fil: Solonin, Sergei A.. N.V. Sklifosovsky Research Institute for Emergency Medicine; Rusia
Fil: Petkov, Stefan. Karolinska Huddinge Hospital. Karolinska Institutet; Suecia
Fil: Nielsen, Morten. Technical University of Denmark; Dinamarca. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto de Investigaciones Biotecnológicas. Universidad Nacional de San Martín. Instituto de Investigaciones Biotecnológicas; Argentina
Fil: Isaguliants, Maria G.. Russian Academy Of Sciences; Rusia. Karolinska Huddinge Hospital. Karolinska Institutet; Suecia
Fil: Mikhailov, Mikhail I.. Russian Medical Academy Of Continuous Professional Education; Rusia. I. I. Mechnikov Research Institute For Vaccines And Sera; Rusia
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.
publishDate 2020
dc.date.none.fl_str_mv 2020-04
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
http://purl.org/coar/resource_type/c_6501
info:ar-repo/semantics/articulo
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv http://hdl.handle.net/11336/112669
Kyuregyan, Karen K.; Kichatova, Vera S.; Karlsen, Anastasiya A.; Isaeva, Olga V.; Solonin, Sergei A.; et al.; Factors influencing the prevalence of resistance-associated substitutions in NS5A protein in treatment-naive patients with chronic hepatitis C; MDPI; Biomedicines; 8; 4; 4-2020; 1-20
2227-9059
CONICET Digital
CONICET
url http://hdl.handle.net/11336/112669
identifier_str_mv Kyuregyan, Karen K.; Kichatova, Vera S.; Karlsen, Anastasiya A.; Isaeva, Olga V.; Solonin, Sergei A.; et al.; Factors influencing the prevalence of resistance-associated substitutions in NS5A protein in treatment-naive patients with chronic hepatitis C; MDPI; Biomedicines; 8; 4; 4-2020; 1-20
2227-9059
CONICET Digital
CONICET
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/url/https://www.mdpi.com/2227-9059/8/4/80
info:eu-repo/semantics/altIdentifier/doi/10.3390/biomedicines8040080
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
eu_rights_str_mv openAccess
rights_invalid_str_mv https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
dc.format.none.fl_str_mv application/pdf
application/pdf
dc.publisher.none.fl_str_mv MDPI
publisher.none.fl_str_mv MDPI
dc.source.none.fl_str_mv reponame:CONICET Digital (CONICET)
instname:Consejo Nacional de Investigaciones Científicas y Técnicas
reponame_str CONICET Digital (CONICET)
collection CONICET Digital (CONICET)
instname_str Consejo Nacional de Investigaciones Científicas y Técnicas
repository.name.fl_str_mv CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicas
repository.mail.fl_str_mv dasensio@conicet.gov.ar; lcarlino@conicet.gov.ar
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score 13.13397

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