Variability and resistance mutations in the hepatitis C virus NS3 protease in patients not treated with protease inhibitors
Autor(a) principal: | |
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Data de Publicação: | 2013 |
Outros Autores: | , , , , |
Tipo de documento: | Artigo |
Idioma: | eng |
Título da fonte: | Repositório Institucional da UNESP |
Texto Completo: | http://dx.doi.org/10.1590/S0074-02762013000100002 http://hdl.handle.net/11449/11553 |
Resumo: | The goal of treatment of chronic hepatitis C is to achieve a sustained virological response, which is defined as exhibiting undetectable hepatitis C virus (HCV) RNA levels in serum following therapy for at least six months. However, the current treatment is only effective in 50% of patients infected with HCV genotype 1, the most prevalent genotype in Brazil. Inhibitors of the serine protease non-structural protein 3 (NS3) have therefore been developed to improve the responses of HCV-infected patients. However, the emergence of drug-resistant variants has been the major obstacle to therapeutic success. The goal of this study was to evaluate the presence of resistance mutations and genetic polymorphisms in the NS3 genomic region of HCV from 37 patients infected with HCV genotype 1 had not been treated with protease inhibitors. Plasma viral RNA was used to amplify and sequence the HCV NS3 gene. The results indicate that the catalytic triad is conserved. A large number of substitutions were observed in codons 153, 40 and 91; the resistant variants T54A, T54S, V55A, R155K and A156T were also detected. This study shows that resistance mutations and genetic polymorphisms are present in the NS3 region of HCV in patients who have not been treated with protease inhibitors, data that are important in determining the efficiency of this new class of drugs in Brazil. |
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Variability and resistance mutations in the hepatitis C virus NS3 protease in patients not treated with protease inhibitorsHCV genotype 1aNS3 protease mutationsprotease inhibitorsThe goal of treatment of chronic hepatitis C is to achieve a sustained virological response, which is defined as exhibiting undetectable hepatitis C virus (HCV) RNA levels in serum following therapy for at least six months. However, the current treatment is only effective in 50% of patients infected with HCV genotype 1, the most prevalent genotype in Brazil. Inhibitors of the serine protease non-structural protein 3 (NS3) have therefore been developed to improve the responses of HCV-infected patients. However, the emergence of drug-resistant variants has been the major obstacle to therapeutic success. The goal of this study was to evaluate the presence of resistance mutations and genetic polymorphisms in the NS3 genomic region of HCV from 37 patients infected with HCV genotype 1 had not been treated with protease inhibitors. Plasma viral RNA was used to amplify and sequence the HCV NS3 gene. The results indicate that the catalytic triad is conserved. A large number of substitutions were observed in codons 153, 40 and 91; the resistant variants T54A, T54S, V55A, R155K and A156T were also detected. This study shows that resistance mutations and genetic polymorphisms are present in the NS3 region of HCV in patients who have not been treated with protease inhibitors, data that are important in determining the efficiency of this new class of drugs in Brazil.Universidade Estadual Paulista Júlio de Mesquita Filho Faculdade de Medicina de Botucatu Divisão HemocentroUniversidade Estadual Paulista Júlio de Mesquita Filho Faculdade de Medicina de Botucatu Departamento de Clínica MédicaUniversidade Estadual Paulista Júlio de Mesquita Filho Faculdade de Medicina de Botucatu Divisão HemocentroUniversidade Estadual Paulista Júlio de Mesquita Filho Faculdade de Medicina de Botucatu Departamento de Clínica MédicaInstituto Oswaldo Cruz, Ministério da SaúdeUniversidade Estadual Paulista (Unesp)Zeminian, Luciana Bonome [UNESP]Padovani, Juliana Lara [UNESP]Corvino, Sílvia Maria [UNESP]Silva, Giovanni Faria [UNESP]Pardini, Maria Ines de Moura Campos [UNESP]Grotto, Rejane Maria Tommasini [UNESP]2014-05-20T13:33:44Z2014-05-20T13:33:44Z2013-02-01info:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/article13-17application/pdfhttp://dx.doi.org/10.1590/S0074-02762013000100002Memórias do Instituto Oswaldo Cruz. Instituto Oswaldo Cruz, Ministério da Saúde, v. 108, n. 1, p. 13-17, 2013.0074-0276http://hdl.handle.net/11449/1155310.1590/S0074-02762013000100002S0074-02762013000100002WOS:000315335800002S0074-02762013000100002.pdf6322604200510676461958833458208477884485643265850000-0002-4035-9486SciELOreponame:Repositório Institucional da UNESPinstname:Universidade Estadual Paulista (UNESP)instacron:UNESPengMemórias do Instituto Oswaldo Cruz2.8331,172info:eu-repo/semantics/openAccess2023-10-23T06:09:21Zoai:repositorio.unesp.br:11449/11553Repositório InstitucionalPUBhttp://repositorio.unesp.br/oai/requestopendoar:29462023-10-23T06:09:21Repositório Institucional da UNESP - Universidade Estadual Paulista (UNESP)false |
dc.title.none.fl_str_mv |
Variability and resistance mutations in the hepatitis C virus NS3 protease in patients not treated with protease inhibitors |
title |
Variability and resistance mutations in the hepatitis C virus NS3 protease in patients not treated with protease inhibitors |
spellingShingle |
Variability and resistance mutations in the hepatitis C virus NS3 protease in patients not treated with protease inhibitors Zeminian, Luciana Bonome [UNESP] HCV genotype 1a NS3 protease mutations protease inhibitors |
title_short |
Variability and resistance mutations in the hepatitis C virus NS3 protease in patients not treated with protease inhibitors |
title_full |
Variability and resistance mutations in the hepatitis C virus NS3 protease in patients not treated with protease inhibitors |
title_fullStr |
Variability and resistance mutations in the hepatitis C virus NS3 protease in patients not treated with protease inhibitors |
title_full_unstemmed |
Variability and resistance mutations in the hepatitis C virus NS3 protease in patients not treated with protease inhibitors |
title_sort |
Variability and resistance mutations in the hepatitis C virus NS3 protease in patients not treated with protease inhibitors |
author |
Zeminian, Luciana Bonome [UNESP] |
author_facet |
Zeminian, Luciana Bonome [UNESP] Padovani, Juliana Lara [UNESP] Corvino, Sílvia Maria [UNESP] Silva, Giovanni Faria [UNESP] Pardini, Maria Ines de Moura Campos [UNESP] Grotto, Rejane Maria Tommasini [UNESP] |
author_role |
author |
author2 |
Padovani, Juliana Lara [UNESP] Corvino, Sílvia Maria [UNESP] Silva, Giovanni Faria [UNESP] Pardini, Maria Ines de Moura Campos [UNESP] Grotto, Rejane Maria Tommasini [UNESP] |
author2_role |
author author author author author |
dc.contributor.none.fl_str_mv |
Universidade Estadual Paulista (Unesp) |
dc.contributor.author.fl_str_mv |
Zeminian, Luciana Bonome [UNESP] Padovani, Juliana Lara [UNESP] Corvino, Sílvia Maria [UNESP] Silva, Giovanni Faria [UNESP] Pardini, Maria Ines de Moura Campos [UNESP] Grotto, Rejane Maria Tommasini [UNESP] |
dc.subject.por.fl_str_mv |
HCV genotype 1a NS3 protease mutations protease inhibitors |
topic |
HCV genotype 1a NS3 protease mutations protease inhibitors |
description |
The goal of treatment of chronic hepatitis C is to achieve a sustained virological response, which is defined as exhibiting undetectable hepatitis C virus (HCV) RNA levels in serum following therapy for at least six months. However, the current treatment is only effective in 50% of patients infected with HCV genotype 1, the most prevalent genotype in Brazil. Inhibitors of the serine protease non-structural protein 3 (NS3) have therefore been developed to improve the responses of HCV-infected patients. However, the emergence of drug-resistant variants has been the major obstacle to therapeutic success. The goal of this study was to evaluate the presence of resistance mutations and genetic polymorphisms in the NS3 genomic region of HCV from 37 patients infected with HCV genotype 1 had not been treated with protease inhibitors. Plasma viral RNA was used to amplify and sequence the HCV NS3 gene. The results indicate that the catalytic triad is conserved. A large number of substitutions were observed in codons 153, 40 and 91; the resistant variants T54A, T54S, V55A, R155K and A156T were also detected. This study shows that resistance mutations and genetic polymorphisms are present in the NS3 region of HCV in patients who have not been treated with protease inhibitors, data that are important in determining the efficiency of this new class of drugs in Brazil. |
publishDate |
2013 |
dc.date.none.fl_str_mv |
2013-02-01 2014-05-20T13:33:44Z 2014-05-20T13:33:44Z |
dc.type.status.fl_str_mv |
info:eu-repo/semantics/publishedVersion |
dc.type.driver.fl_str_mv |
info:eu-repo/semantics/article |
format |
article |
status_str |
publishedVersion |
dc.identifier.uri.fl_str_mv |
http://dx.doi.org/10.1590/S0074-02762013000100002 Memórias do Instituto Oswaldo Cruz. Instituto Oswaldo Cruz, Ministério da Saúde, v. 108, n. 1, p. 13-17, 2013. 0074-0276 http://hdl.handle.net/11449/11553 10.1590/S0074-02762013000100002 S0074-02762013000100002 WOS:000315335800002 S0074-02762013000100002.pdf 6322604200510676 4619588334582084 7788448564326585 0000-0002-4035-9486 |
url |
http://dx.doi.org/10.1590/S0074-02762013000100002 http://hdl.handle.net/11449/11553 |
identifier_str_mv |
Memórias do Instituto Oswaldo Cruz. Instituto Oswaldo Cruz, Ministério da Saúde, v. 108, n. 1, p. 13-17, 2013. 0074-0276 10.1590/S0074-02762013000100002 S0074-02762013000100002 WOS:000315335800002 S0074-02762013000100002.pdf 6322604200510676 4619588334582084 7788448564326585 0000-0002-4035-9486 |
dc.language.iso.fl_str_mv |
eng |
language |
eng |
dc.relation.none.fl_str_mv |
Memórias do Instituto Oswaldo Cruz 2.833 1,172 |
dc.rights.driver.fl_str_mv |
info:eu-repo/semantics/openAccess |
eu_rights_str_mv |
openAccess |
dc.format.none.fl_str_mv |
13-17 application/pdf |
dc.publisher.none.fl_str_mv |
Instituto Oswaldo Cruz, Ministério da Saúde |
publisher.none.fl_str_mv |
Instituto Oswaldo Cruz, Ministério da Saúde |
dc.source.none.fl_str_mv |
SciELO reponame:Repositório Institucional da UNESP instname:Universidade Estadual Paulista (UNESP) instacron:UNESP |
instname_str |
Universidade Estadual Paulista (UNESP) |
instacron_str |
UNESP |
institution |
UNESP |
reponame_str |
Repositório Institucional da UNESP |
collection |
Repositório Institucional da UNESP |
repository.name.fl_str_mv |
Repositório Institucional da UNESP - Universidade Estadual Paulista (UNESP) |
repository.mail.fl_str_mv |
|
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1799964671336251392 |