The presence of resistance mutations to protease and polymerase inhibitors in Hepatitis C virus sequences from the Los Alamos databank

Detalhes bibliográficos
Autor(a) principal: Alves, Rafael
Data de Publicação: 2013
Outros Autores: Queiroz, Artur Trancoso Lopo de, Pessoa, Mario Guimarães, Silva, E. F. da, Mazo, Daniel Ferraz de Campos, Carrilho, Flair José, Carvalho-Filho, R. J, Carvalho, Isabel Maria Vicente Guedes de
Tipo de documento: Artigo
Idioma: eng
Título da fonte: Repositório Institucional da FIOCRUZ (ARCA)
Texto Completo: https://www.arca.fiocruz.br/handle/icict/8792
Resumo: Universidade Federal de São Paulo. Laboratório de Hepatologia Molecular Aplicada. Divisão de Gastroenterologia. Sao Paulo, SP, Brasil
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spelling Alves, RafaelQueiroz, Artur Trancoso Lopo dePessoa, Mario GuimarãesSilva, E. F. daMazo, Daniel Ferraz de CamposCarrilho, Flair JoséCarvalho-Filho, R. JCarvalho, Isabel Maria Vicente Guedes de2014-11-11T18:22:01Z2014-11-11T18:22:01Z2013ALVES, R. et al. The presence of resistance mutations to protease and polymerase inhibitors in Hepatitis C virus sequences from the Los Alamos databank. Journal of Viral Hepatitis, v. 20, n. 6, p. 414-421, 2013.1365-2893https://www.arca.fiocruz.br/handle/icict/879210.1111/jvh.12051engJohn Wiley & Sons LtdThe presence of resistance mutations to protease and polymerase inhibitors in Hepatitis C virus sequences from the Los Alamos databankinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleUniversidade Federal de São Paulo. Laboratório de Hepatologia Molecular Aplicada. Divisão de Gastroenterologia. Sao Paulo, SP, BrasilFundação Oswaldo Cruz. Centro de Pesquisas Gonçalo Moniz. Laboratório de Immunoparasitologia. Salvador, BA, BrasilUniversity of Sao Paulo School of Medicine. Department of Gastroenterology. Sao Paulo, SP, BrasilUniversity of Sao Paulo School of Medicine. Department of Gastroenterology. Sao Paulo, SP, BrasilUniversity of Sao Paulo School of Medicine. Department of Gastroenterology. Sao Paulo, SP, BrasilUniversity of Sao Paulo School of Medicine. Department of Gastroenterology. Sao Paulo, SP, BrasilUniversidade Federal de São Paulo. Laboratório de Hepatologia Molecular Aplicada. Divisão de Gastroenterologia. Sao Paulo, SP, BrasilUniversidade Federal de São Paulo. Laboratório de Hepatologia Molecular Aplicada. Divisão de Gastroenterologia. Sao Paulo, SP, Brasil / Instituto Butantan. Imunologia Viral. Sao Paulo, SP, BrasilSeveral new direct-acting antiviral (DAA) drugs are in development for chronic hepatitis C viral (HCV) infection, and NS3-NS4A serine protease and the NS5B RNA-dependent RNA polymerase have been the major targets. HCV variants displaying drug-resistant phenotypes have been observed both in vitro and during clinical trials. Our aim was to characterize amino acid changes at positions previously associated with resistance in protease (NS3) and polymerase (NS5B) regions from treatment-naïve HCV patients infected with genotypes 1a, 1b and 3a. All 1383 NS3 protease sequences (genotype 1a = 680, 1b = 498 and 3a = 205) and 806 NS5B polymerase sequences (genotypes 1a = 471, 1b = 329, 3a = 6) were collected from Los Alamos databank. Genotype 3a protease sequences showed the typical low-level resistance mutation V36L. NS3 sequences from other genotypes presented mutations on positions 36, 39, 41, 43, 54, 80, 109, 155 and 168 in a frequency lower than 2%, except for the mutation Q80R found in 35% of genotype 1a isolates. Polymerase sequences from genotype 3a patients showed five typical mutations: L419I, I424V, I482L, V499A and S556G. Two positions presented high polymorphism in the NS5B region from genotype 1a (V499A) and genotype 1b (C316N) subjects. Our results demonstrated a natural profile of genotype 3a that can be associated with the pre-existence of HCV variants resistant to first-generation protease inhibitors and to non-nucleoside polymerase inhibitors. Likewise, genotype 1b isolates and genotype 1a sequences exhibited pre-existing mutations associated with resistance to Palm II and Thumb I polymerase inhibitors, respectively.Direct-acting antiviral agentsHepatitis C virusPolymeraseProteaseResistance mutationsFarmacorresistência ViralHepacivirus/genéticaInibidores de Proteases/farmacologiaProteínas não Estruturais Virais/genéticaSubstituição de AminoácidosAntivirais/farmacologiaSequência de BasesDomínio CatalíticoBases de Dados GenéticasGenótipoHepacivirus/efeitos de drogasHepacivirus/enzimologiaHepatite C Crônica/quimioterapiaHumanosTaxa de MutaçãoProteínas não Estruturais Virais/antagonistas & inibidoresinfo:eu-repo/semantics/openAccessreponame:Repositório Institucional da FIOCRUZ (ARCA)instname:Fundação Oswaldo Cruz (FIOCRUZ)instacron:FIOCRUZLICENSElicense.txtlicense.txttext/plain; charset=utf-81914https://www.arca.fiocruz.br/bitstream/icict/8792/1/license.txt7d48279ffeed55da8dfe2f8e81f3b81fMD51ORIGINALAlves R The presence....pdfAlves R The presence....pdfapplication/pdf88249https://www.arca.fiocruz.br/bitstream/icict/8792/2/Alves%20R%20The%20presence....pdf80e7d243ecb07e377a49802c1d37967eMD52TEXTAlves R The presence....pdf.txtAlves R The presence....pdf.txtExtracted texttext/plain36820https://www.arca.fiocruz.br/bitstream/icict/8792/3/Alves%20R%20The%20presence....pdf.txt6a4a0485ba90535af4f5435b83ce6e97MD53icict/87922023-03-15 14:32:54.066oai:www.arca.fiocruz.br:icict/8792TElDRU7Dh0EgREUgRElTVFJJQlVJw4fDg08gTsODTy1FWENMVVNJVkEKCkFvIGNvbmNvcmRhciBlIGFjZWl0YXIgZXN0YSBsaWNlbsOnYSB2b2PDqiAoYXV0b3Igb3UgZGV0ZW50b3IgZG9zIGRpcmVpdG9zIGF1dG9yYWlzKToKCmEpIERlY2xhcmEgcXVlIGNvbmhlY2UgYSBwb2zDrXRpY2EgZGUgY29weXJpZ2h0IGRhIGVkaXRvcmEgZG8gc2V1IGRvY3VtZW50by4KCmIpIERlY2xhcmEgcXVlIGNvbmhlY2UgZSBhY2VpdGEgYXMgRGlyZXRyaXplcyBwYXJhIG8gUmVwb3NpdMOzcmlvIEluc3RpdHVjaW9uYWwgZGEgRnVuZGHDp8OjbyBPc3dhbGRvIENydXogKEZJT0NSVVopLgoKYykgQ29uY2VkZSDDoCBGSU9DUlVaIG8gZGlyZWl0byBuw6NvLWV4Y2x1c2l2byBkZSBhcnF1aXZhciwgcmVwcm9kdXppciwgY29udmVydGVyIChjb21vIGRlZmluaWRvIGEgc2VndWlyKSwgY29tdW5pY2FyCiAKZS9vdSBkaXN0cmlidWlyIG5vIFJlcG9zaXTDs3JpbyBkYSBGSU9DUlVaLCBvIGRvY3VtZW50byBlbnRyZWd1ZSAoaW5jbHVpbmRvIG8gcmVzdW1vL2Fic3RyYWN0KSBlbSBmb3JtYXRvIGRpZ2l0YWwgb3UgCgpwb3IgcXVhbHF1ZXIgb3V0cm8gbWVpby4KCmQpIERlY2xhcmEgcXVlIGF1dG9yaXphIGEgRklPQ1JVWiBhIGFycXVpdmFyIG1haXMgZGUgdW1hIGPDs3BpYSBkZXN0ZSBkb2N1bWVudG8gZSBjb252ZXJ0w6otbG8sIHNlbSBhbHRlcmFyIG8gc2V1IGNvbnRlw7pkbywgCgpwYXJhIHF1YWxxdWVyIGZvcm1hdG8gZGUgYXJxdWl2bywgbWVpbyBvdSBzdXBvcnRlLCBwYXJhIGVmZWl0b3MgZGUgc2VndXJhbsOnYSwgcHJlc2VydmHDp8OjbyAoYmFja3VwKSBlIGFjZXNzby4KCmUpIERlY2xhcmEgcXVlIG8gZG9jdW1lbnRvIHN1Ym1ldGlkbyDDqSBvIHNldSB0cmFiYWxobyBvcmlnaW5hbCwgZSBxdWUgZGV0w6ltIG8gZGlyZWl0byBkZSBjb25jZWRlciBhIHRlcmNlaXJvcyBvcyBkaXJlaXRvcyAKCmNvbnRpZG9zIG5lc3RhIGxpY2Vuw6dhLiBEZWNsYXJhIHRhbWLDqW0gcXVlIGEgZW50cmVnYSBkbyBkb2N1bWVudG8gbsOjbyBpbmZyaW5nZSBvcyBkaXJlaXRvcyBkZSBxdWFscXVlciBvdXRyYSBwZXNzb2Egb3UgZW50aWRhZGUuCgpmKSBEZWNsYXJhIHF1ZSwgbm8gY2FzbyBkbyBkb2N1bWVudG8gc3VibWV0aWRvIGNvbnRlciBtYXRlcmlhbCBkbyBxdWFsIG7Do28gZGV0w6ltIG9zIGRpcmVpdG9zIGRlIGF1dG9yLCBvYnRldmUgYSBhdXRvcml6YcOnw6NvIAoKaXJyZXN0cml0YSBkbyByZXNwZWN0aXZvIGRldGVudG9yIGRlc3NlcyBkaXJlaXRvcywgcGFyYSBjZWRlciBhIEZJT0NSVVogb3MgZGlyZWl0b3MgcmVxdWVyaWRvcyBwb3IgZXN0YSBMaWNlbsOnYSBlIGF1dG9yaXphciBhIAoKdXRpbGl6w6EtbG9zIGxlZ2FsbWVudGUuIERlY2xhcmEgdGFtYsOpbSBxdWUgZXNzZSBtYXRlcmlhbCBjdWpvcyBkaXJlaXRvcyBzw6NvIGRlIHRlcmNlaXJvcyBlc3TDoSBjbGFyYW1lbnRlIGlkZW50aWZpY2FkbyBlIHJlY29uaGVjaWRvIAoKbm8gdGV4dG8gb3UgY29udGXDumRvIGRvIGRvY3VtZW50byBlbnRyZWd1ZS4KCmcpIFNFIE8gRE9DVU1FTlRPIEVOVFJFR1VFIMOJIEJBU0VBRE8gRU0gVFJBQkFMSE8gRklOQU5DSUFETyBPVSBBUE9JQURPIFBPUiBPVVRSQSBJTlNUSVRVScOHw4NPIFFVRSBOw4NPIEEgRklPQ1JVWiwgREVDTEFSQSBRVUUgQ1VNUFJJVSAKClFVQUlTUVVFUiBPQlJJR0HDh8OVRVMgRVhJR0lEQVMgUEVMTyBSRVNQRUNUSVZPIENPTlRSQVRPIE9VIEFDT1JETy4gQSBGSU9DUlVaIGlkZW50aWZpY2Fyw6EgY2xhcmFtZW50ZSBvKHMpIG5vbWUocykgZG8ocykgYXV0b3IoZXMpIGRvcyAKCmRpcmVpdG9zIGRvIGRvY3VtZW50byBlbnRyZWd1ZSBlIG7Do28gZmFyw6EgcXVhbHF1ZXIgYWx0ZXJhw6fDo28sIHBhcmEgYWzDqW0gZG8gcHJldmlzdG8gbmEgYWzDrW5lYSBjKS4KRepositório InstitucionalPUBhttps://www.arca.fiocruz.br/oai/requestrepositorio.arca@fiocruz.bropendoar:21352023-03-15T17:32:54Repositório Institucional da FIOCRUZ (ARCA) - Fundação Oswaldo Cruz (FIOCRUZ)false
dc.title.pt_BR.fl_str_mv The presence of resistance mutations to protease and polymerase inhibitors in Hepatitis C virus sequences from the Los Alamos databank
title The presence of resistance mutations to protease and polymerase inhibitors in Hepatitis C virus sequences from the Los Alamos databank
spellingShingle The presence of resistance mutations to protease and polymerase inhibitors in Hepatitis C virus sequences from the Los Alamos databank
Alves, Rafael
Direct-acting antiviral agents
Hepatitis C virus
Polymerase
Protease
Resistance mutations
Farmacorresistência Viral
Hepacivirus/genética
Inibidores de Proteases/farmacologia
Proteínas não Estruturais Virais/genética
Substituição de Aminoácidos
Antivirais/farmacologia
Sequência de Bases
Domínio Catalítico
Bases de Dados Genéticas
Genótipo
Hepacivirus/efeitos de drogas
Hepacivirus/enzimologia
Hepatite C Crônica/quimioterapia
Humanos
Taxa de Mutação
Proteínas não Estruturais Virais/antagonistas & inibidores
title_short The presence of resistance mutations to protease and polymerase inhibitors in Hepatitis C virus sequences from the Los Alamos databank
title_full The presence of resistance mutations to protease and polymerase inhibitors in Hepatitis C virus sequences from the Los Alamos databank
title_fullStr The presence of resistance mutations to protease and polymerase inhibitors in Hepatitis C virus sequences from the Los Alamos databank
title_full_unstemmed The presence of resistance mutations to protease and polymerase inhibitors in Hepatitis C virus sequences from the Los Alamos databank
title_sort The presence of resistance mutations to protease and polymerase inhibitors in Hepatitis C virus sequences from the Los Alamos databank
author Alves, Rafael
author_facet Alves, Rafael
Queiroz, Artur Trancoso Lopo de
Pessoa, Mario Guimarães
Silva, E. F. da
Mazo, Daniel Ferraz de Campos
Carrilho, Flair José
Carvalho-Filho, R. J
Carvalho, Isabel Maria Vicente Guedes de
author_role author
author2 Queiroz, Artur Trancoso Lopo de
Pessoa, Mario Guimarães
Silva, E. F. da
Mazo, Daniel Ferraz de Campos
Carrilho, Flair José
Carvalho-Filho, R. J
Carvalho, Isabel Maria Vicente Guedes de
author2_role author
author
author
author
author
author
author
dc.contributor.author.fl_str_mv Alves, Rafael
Queiroz, Artur Trancoso Lopo de
Pessoa, Mario Guimarães
Silva, E. F. da
Mazo, Daniel Ferraz de Campos
Carrilho, Flair José
Carvalho-Filho, R. J
Carvalho, Isabel Maria Vicente Guedes de
dc.subject.en.pt_BR.fl_str_mv Direct-acting antiviral agents
Hepatitis C virus
Polymerase
Protease
Resistance mutations
topic Direct-acting antiviral agents
Hepatitis C virus
Polymerase
Protease
Resistance mutations
Farmacorresistência Viral
Hepacivirus/genética
Inibidores de Proteases/farmacologia
Proteínas não Estruturais Virais/genética
Substituição de Aminoácidos
Antivirais/farmacologia
Sequência de Bases
Domínio Catalítico
Bases de Dados Genéticas
Genótipo
Hepacivirus/efeitos de drogas
Hepacivirus/enzimologia
Hepatite C Crônica/quimioterapia
Humanos
Taxa de Mutação
Proteínas não Estruturais Virais/antagonistas & inibidores
dc.subject.decs.pt_BR.fl_str_mv Farmacorresistência Viral
Hepacivirus/genética
Inibidores de Proteases/farmacologia
Proteínas não Estruturais Virais/genética
Substituição de Aminoácidos
Antivirais/farmacologia
Sequência de Bases
Domínio Catalítico
Bases de Dados Genéticas
Genótipo
Hepacivirus/efeitos de drogas
Hepacivirus/enzimologia
Hepatite C Crônica/quimioterapia
Humanos
Taxa de Mutação
Proteínas não Estruturais Virais/antagonistas & inibidores
description Universidade Federal de São Paulo. Laboratório de Hepatologia Molecular Aplicada. Divisão de Gastroenterologia. Sao Paulo, SP, Brasil
publishDate 2013
dc.date.issued.fl_str_mv 2013
dc.date.accessioned.fl_str_mv 2014-11-11T18:22:01Z
dc.date.available.fl_str_mv 2014-11-11T18:22:01Z
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 ALVES, R. et al. The presence of resistance mutations to protease and polymerase inhibitors in Hepatitis C virus sequences from the Los Alamos databank. Journal of Viral Hepatitis, v. 20, n. 6, p. 414-421, 2013.
dc.identifier.uri.fl_str_mv https://www.arca.fiocruz.br/handle/icict/8792
dc.identifier.issn.none.fl_str_mv 1365-2893
dc.identifier.doi.none.fl_str_mv 10.1111/jvh.12051
identifier_str_mv ALVES, R. et al. The presence of resistance mutations to protease and polymerase inhibitors in Hepatitis C virus sequences from the Los Alamos databank. Journal of Viral Hepatitis, v. 20, n. 6, p. 414-421, 2013.
1365-2893
10.1111/jvh.12051
url https://www.arca.fiocruz.br/handle/icict/8792
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 John Wiley & Sons Ltd
publisher.none.fl_str_mv John Wiley & Sons Ltd
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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