Protease inhibitor resistance mutations in untreated Brazilian patients infected with HCV: Novel insights about targeted genotyping approaches.

Butantan Institute. Viral Imunology. São Paulo, SP, Brasil / Applied Molecular Hepatology Laboratory. LHeMA. Hepatitis Sector. Gastroenterology Division. São Paulo, SP, Brasil

Detalhes bibliográficos
Autores: Carvalho, Isabel Maria Vicente Guedes de, Silva, Rafael Alves da, Souza, Polyana A. Vasconcelos Medeiros de, Silva, Edvaldo F. da, Mazo, Daniel Ferraz de Campos, Carrilho, Flair José, Queiroz, Artur Trancoso Lopo de, Pessoa, Mario Guimarães
Formato: artículo
Estado:Versión publicada
Fecha de publicación:2014
País:Brasil
Recursos:Fundação Oswaldo Cruz (FIOCRUZ)
Repositorio:Repositório Institucional da FIOCRUZ (ARCA)
Idioma:inglés
OAI Identifier:oai:arca.fiocruz.br:icict/8464
Acesso em linha:https://arca.fiocruz.br/handle/icict/8464
Access Level:acceso abierto
Palavra-chave:HCV
Hepatitis C
Protease inhibitors
Resistance
Genotyping
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dc.title.none.fl_str_mv Protease inhibitor resistance mutations in untreated Brazilian patients infected with HCV: Novel insights about targeted genotyping approaches.
title Protease inhibitor resistance mutations in untreated Brazilian patients infected with HCV: Novel insights about targeted genotyping approaches.
spellingShingle Protease inhibitor resistance mutations in untreated Brazilian patients infected with HCV: Novel insights about targeted genotyping approaches.
Carvalho, Isabel Maria Vicente Guedes de
HCV
Hepatitis C
Protease inhibitors
Resistance
Genotyping
title_short Protease inhibitor resistance mutations in untreated Brazilian patients infected with HCV: Novel insights about targeted genotyping approaches.
title_full Protease inhibitor resistance mutations in untreated Brazilian patients infected with HCV: Novel insights about targeted genotyping approaches.
title_fullStr Protease inhibitor resistance mutations in untreated Brazilian patients infected with HCV: Novel insights about targeted genotyping approaches.
title_full_unstemmed Protease inhibitor resistance mutations in untreated Brazilian patients infected with HCV: Novel insights about targeted genotyping approaches.
title_sort Protease inhibitor resistance mutations in untreated Brazilian patients infected with HCV: Novel insights about targeted genotyping approaches.
dc.creator.none.fl_str_mv Carvalho, Isabel Maria Vicente Guedes de
Silva, Rafael Alves da
Souza, Polyana A. Vasconcelos Medeiros de
Silva, Edvaldo F. da
Mazo, Daniel Ferraz de Campos
Carrilho, Flair José
Queiroz, Artur Trancoso Lopo de
Pessoa, Mario Guimarães
author Carvalho, Isabel Maria Vicente Guedes de
author_facet Carvalho, Isabel Maria Vicente Guedes de
Silva, Rafael Alves da
Souza, Polyana A. Vasconcelos Medeiros de
Silva, Edvaldo F. da
Mazo, Daniel Ferraz de Campos
Carrilho, Flair José
Queiroz, Artur Trancoso Lopo de
Pessoa, Mario Guimarães
author_role author
author2 Silva, Rafael Alves da
Souza, Polyana A. Vasconcelos Medeiros de
Silva, Edvaldo F. da
Mazo, Daniel Ferraz de Campos
Carrilho, Flair José
Queiroz, Artur Trancoso Lopo de
Pessoa, Mario Guimarães
author2_role author
author
author
author
author
author
author
dc.subject.en.none.fl_str_mv HCV
Hepatitis C
Protease inhibitors
Resistance
Genotyping
topic HCV
Hepatitis C
Protease inhibitors
Resistance
Genotyping
description Butantan Institute. Viral Imunology. São Paulo, SP, Brasil / Applied Molecular Hepatology Laboratory. LHeMA. Hepatitis Sector. Gastroenterology Division. São Paulo, SP, Brasil
publishDate 2014
dc.date.accessioned.fl_str_mv 2014-09-29T13:55:12Z
dc.date.available.fl_str_mv 2014-09-29T13:55:12Z
dc.date.issued.fl_str_mv 2014
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.citation.fl_str_mv CARVALHO, I. M. V. G et al. Protease inhibitor resistance mutations in untreated Brazilian patients infected with HCV: Novel insights about targeted genotyping approaches. Journal of Medical Virology, v. 86, n. 10, p. 1714-1721, 2014.
dc.identifier.uri.fl_str_mv https://arca.fiocruz.br/handle/icict/8464
dc.identifier.issn.none.fl_str_mv 1096-9071
dc.identifier.doi.none.fl_str_mv 10.1002/jmv.24015
identifier_str_mv CARVALHO, I. M. V. G et al. Protease inhibitor resistance mutations in untreated Brazilian patients infected with HCV: Novel insights about targeted genotyping approaches. Journal of Medical Virology, v. 86, n. 10, p. 1714-1721, 2014.
1096-9071
10.1002/jmv.24015
url https://arca.fiocruz.br/handle/icict/8464
dc.language.iso.fl_str_mv eng
language eng
dc.rights.driver.fl_str_mv info:eu-repo/semantics/openAccess
eu_rights_str_mv openAccess
dc.publisher.none.fl_str_mv Wiley Periodicals Inc.
publisher.none.fl_str_mv Wiley Periodicals Inc.
dc.source.none.fl_str_mv reponame:Repositório Institucional da FIOCRUZ (ARCA)
instname:Fundação Oswaldo Cruz (FIOCRUZ)
instacron:FIOCRUZ
instname_str Fundação Oswaldo Cruz (FIOCRUZ)
instacron_str FIOCRUZ
institution FIOCRUZ
reponame_str Repositório Institucional da FIOCRUZ (ARCA)
collection Repositório Institucional da FIOCRUZ (ARCA)
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spelling 2014-09-29T13:55:12Z2014-09-29T13:55:12Z2014CARVALHO, I. M. V. G et al. Protease inhibitor resistance mutations in untreated Brazilian patients infected with HCV: Novel insights about targeted genotyping approaches. Journal of Medical Virology, v. 86, n. 10, p. 1714-1721, 2014.1096-9071https://arca.fiocruz.br/handle/icict/846410.1002/jmv.24015engWiley Periodicals Inc.Protease inhibitor resistance mutations in untreated Brazilian patients infected with HCV: Novel insights about targeted genotyping approaches.info:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleButantan Institute. Viral Imunology. São Paulo, SP, Brasil / Applied Molecular Hepatology Laboratory. LHeMA. Hepatitis Sector. Gastroenterology Division. São Paulo, SP, BrasilApplied Molecular Hepatology Laboratory. LHeMA. Hepatitis Sector. Gastroenterology Division. São Paulo, SP, BrasilButantan Institute. Viral Imunology. São Paulo, SP, Brasil / Applied Molecular Hepatology Laboratory. LHeMA. Hepatitis Sector. Gastroenterology Division. São Paulo, SP, BrasilUniversity of São Paulo School of Medicine. Department of Gastroenterology. São Paulo, SP, BrasilUniversity of São Paulo School of Medicine. Department of Gastroenterology. São Paulo, SP, BrasilUniversity of São Paulo School of Medicine. Department of Gastroenterology. São Paulo, SP, BrasilFundação Oswaldo Cruz. Centro de Pesquisa Gonçalo Moniz. Salvador, BA, BrasilUniversity of São Paulo School of Medicine. Department of Gastroenterology. São Paulo, SP, BrasilSeveral new direct-acting antiviral (DAA) drugs are being developed or are already approved for the treatment of chronic hepatitis C virus (HCV) infection. HCV variants presenting drug-resistant phenotypes were observed both in vitro and during clinical trials. The aim of this study was to characterize amino acid changes at positions previously associated with resistance in the NS3 protease in untreated Brazilian patients infected with HCV genotypes 1a and 1b. Plasma samples from 171 untreated Brazilian patients infected with HCV were obtained from the Department of Gastroenterology of Clinics Hospital (HCFMUSP) in São Paulo, Brazil. Nested PCR and Sanger sequencing were used to obtain genetic information on the NS3 protein. Bioinformatics was used to confirm subtype information and analyze frequencies of resistance mutations. The results from the genotype analysis using non-NS3 targeted methods were at variance with those obtained from the NS3 protease phylogenetic analyses. It was found that 7.4% of patients infected with HCV genotype 1a showed the resistance-associated mutations V36L, T54S, Q80K, and R155K, while 5.1% of patients infected with HCV genotype 1b had the resistance-associated mutations V36L, Q41R, T54S, and D168S. Notably, codons at positions 80 and 155 differed between samples from Brazilian patient used in this study and global isolates. The present study demonstrates that genotyping methods targeting the NS3 protein showed a difference of results when compared to mainstream methodologies (INNO-LiPA and polymerase sequencing). The resistance mutations present in untreated patients infected with HCV and codon composition bias by geographical location warrant closer examination.HCVHepatitis CProtease inhibitorsResistanceGenotypinginfo:eu-repo/semantics/openAccessreponame:Repositório Institucional da FIOCRUZ (ARCA)instname:Fundação Oswaldo Cruz (FIOCRUZ)instacron:FIOCRUZCarvalho, Isabel Maria Vicente Guedes deSilva, Rafael Alves daSouza, Polyana A. Vasconcelos Medeiros deSilva, Edvaldo F. daMazo, Daniel Ferraz de CamposCarrilho, Flair JoséQueiroz, Artur Trancoso Lopo dePessoa, Mario GuimarãesLICENSElicense.txtlicense.txttext/plain; charset=utf-81914https://arca.fiocruz.br/bitstreams/197baaa4-bdfc-474d-8a58-b779dda1f502/download7d48279ffeed55da8dfe2f8e81f3b81fMD51falseAnonymousREADORIGINALCarvalho IMVG Protease inhibitor....pdfCarvalho IMVG Protease inhibitor....pdfapplication/pdf1106740https://arca.fiocruz.br/bitstreams/845d338f-d27b-45f9-930e-0735968c9c62/downloadb46c977078fa7e9aafa08ccb325a33e4MD52trueAnonymousREADTEXTCarvalho IMVG Protease inhibitor....pdf.txtCarvalho IMVG Protease inhibitor....pdf.txtExtracted texttext/plain35674https://arca.fiocruz.br/bitstreams/0c66f085-9687-41ef-852c-e416d82726f2/download5001db118407f36edd1c86bda44b6468MD511falseAnonymousREADTHUMBNAILCarvalho IMVG Protease inhibitor....pdf.jpgCarvalho IMVG Protease inhibitor....pdf.jpgGenerated Thumbnailimage/jpeg46804https://arca.fiocruz.br/bitstreams/ffcc58de-7f0b-4385-8cfb-ba614338c581/download6671f350fb92e3688df55a9544292d90MD512falseAnonymousREADicict/84642025-12-10 14:28:39.249open.accessoai:arca.fiocruz.br:icict/8464https://arca.fiocruz.brRepositório InstitucionalPUBhttps://www.arca.fiocruz.br/oai/requestrepositorio.arca@fiocruz.bropendoar:21352025-12-10T17:28:39Repositório Institucional da FIOCRUZ (ARCA) - Fundação Oswaldo Cruz (FIOCRUZ)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
score 15,301629

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