Genetic diversity of NS3 protease from Brazilian HCV isolates and possible implications for therapy with direct-acting antiviral drugs

Detalhes bibliográficos
Autor(a) principal: Silva, Allan Peres da
Data de Publicação: 2012
Outros Autores: Almeida, Adilson José de, Lampe, Elisabeth
Tipo de documento: Artigo
Idioma: eng
Título da fonte: Repositório Institucional da FIOCRUZ (ARCA)
Texto Completo: https://www.arca.fiocruz.br/handle/icict/16867
Resumo: Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Hepatites Virais. Rio de Janeiro, RJ. Brasil.
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spelling Silva, Allan Peres daAlmeida, Adilson José deLampe, Elisabeth2017-01-17T14:31:33Z2017-01-17T14:31:33Z2012SILVA, Allan Peres da; ALMEIDA, Adilson José de; LAMPE, Elisabeth. Genetic diversity of NS3 protease from Brazilian HCV isolates and possible implications for therapy with direct-acting antiviral drugs. Mem Inst Oswaldo Cruz, v.107, n.2, p.254-261, Mar. 2012.0074-0276https://www.arca.fiocruz.br/handle/icict/168671678-8060engFundação Oswaldo Cruz. Instituto Oswaldo CruzDiversidade genéticaVírus da hepatite CProteaseAgentes antivirais de ação diretagenetic diversityNS3 proteasehepatitis C virusdirect-acting antiviral agentsGenetic diversity of NS3 protease from Brazilian HCV isolates and possible implications for therapy with direct-acting antiviral drugsinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleFundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Hepatites Virais. Rio de Janeiro, RJ. Brasil.Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Hepatites Virais. Rio de Janeiro, RJ. Brasil / Universidade Federal do Estado do Rio de Janeiro. Hospital Universitário Gaffrée Guinle. Rio de Janeiro, RJ, Brasil.Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Hepatites Virais. Rio de Janeiro, RJ. Brasil.The hepatitis C virus (HCV) NS3 protease has been one of the molecular targets of new therapeutic approaches. Its genomic sequence variability in Brazilian HCV isolates is poorly documented. To obtain more information on the magnitude of its genetic diversity, 114 Brazilian HCV samples were sequenced and analysed together with global reference sequences. Genetic distance (d) analyses revealed that subtype 1b had a higher degree of heterogeneity (d = 0.098) than subtypes 1a (d = 0.060) and 3a (d = 0.062). Brazilian isolates of subtype 1b were distributed in the phylogenetic tree among sequences from other countries, whereas most subtype 1a and 3a sequences clustered into a single branch. Additional characterisation of subtype 1a in clades 1 and 2 revealed that all but two Brazilian subtype 1a sequences formed a distinct and strongly supported (approximate likelihood-ratio test = 93) group of sequences inside clade 1. Moreover, this subcluster inside clade 1 presented an unusual phenotypic characteristic in relation to the presence of resistance mutations for macrocyclic inhibitors. In particular, the mutation Q80K was found in the majority of clade 1 sequences, but not in the Brazilian isolates. These data demonstrate that Brazilian HCV subtypes display a distinct pattern of genetic diversity and reinforce the importance of sequence information in future therapeutic approaches.info:eu-repo/semantics/openAccessreponame:Repositório Institucional da FIOCRUZ (ARCA)instname:Fundação Oswaldo Cruz (FIOCRUZ)instacron:FIOCRUZLICENSElicense.txtlicense.txttext/plain; charset=utf-82991https://www.arca.fiocruz.br/bitstream/icict/16867/1/license.txt5a560609d32a3863062d77ff32785d58MD51ORIGINALallan_silva_etal_IOC_2012.pdfallan_silva_etal_IOC_2012.pdfapplication/pdf757219https://www.arca.fiocruz.br/bitstream/icict/16867/2/allan_silva_etal_IOC_2012.pdf6d3f98ef06f8832ef5cf7fb8614bcdbdMD52TEXTallan_silva_etal_IOC_2012.pdf.txtallan_silva_etal_IOC_2012.pdf.txtExtracted texttext/plain38751https://www.arca.fiocruz.br/bitstream/icict/16867/3/allan_silva_etal_IOC_2012.pdf.txt241d8ac62fdf59d511cabb493754dcaaMD53icict/168672018-08-15 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dc.title.pt_BR.fl_str_mv Genetic diversity of NS3 protease from Brazilian HCV isolates and possible implications for therapy with direct-acting antiviral drugs
title Genetic diversity of NS3 protease from Brazilian HCV isolates and possible implications for therapy with direct-acting antiviral drugs
spellingShingle Genetic diversity of NS3 protease from Brazilian HCV isolates and possible implications for therapy with direct-acting antiviral drugs
Silva, Allan Peres da
Diversidade genética
Vírus da hepatite C
Protease
Agentes antivirais de ação direta
genetic diversity
NS3 protease
hepatitis C virus
direct-acting antiviral agents
title_short Genetic diversity of NS3 protease from Brazilian HCV isolates and possible implications for therapy with direct-acting antiviral drugs
title_full Genetic diversity of NS3 protease from Brazilian HCV isolates and possible implications for therapy with direct-acting antiviral drugs
title_fullStr Genetic diversity of NS3 protease from Brazilian HCV isolates and possible implications for therapy with direct-acting antiviral drugs
title_full_unstemmed Genetic diversity of NS3 protease from Brazilian HCV isolates and possible implications for therapy with direct-acting antiviral drugs
title_sort Genetic diversity of NS3 protease from Brazilian HCV isolates and possible implications for therapy with direct-acting antiviral drugs
author Silva, Allan Peres da
author_facet Silva, Allan Peres da
Almeida, Adilson José de
Lampe, Elisabeth
author_role author
author2 Almeida, Adilson José de
Lampe, Elisabeth
author2_role author
author
dc.contributor.author.fl_str_mv Silva, Allan Peres da
Almeida, Adilson José de
Lampe, Elisabeth
dc.subject.other.pt_BR.fl_str_mv Diversidade genética
Vírus da hepatite C
Protease
Agentes antivirais de ação direta
topic Diversidade genética
Vírus da hepatite C
Protease
Agentes antivirais de ação direta
genetic diversity
NS3 protease
hepatitis C virus
direct-acting antiviral agents
dc.subject.en.pt_BR.fl_str_mv genetic diversity
NS3 protease
hepatitis C virus
direct-acting antiviral agents
description Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Hepatites Virais. Rio de Janeiro, RJ. Brasil.
publishDate 2012
dc.date.issued.fl_str_mv 2012
dc.date.accessioned.fl_str_mv 2017-01-17T14:31:33Z
dc.date.available.fl_str_mv 2017-01-17T14:31:33Z
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 SILVA, Allan Peres da; ALMEIDA, Adilson José de; LAMPE, Elisabeth. Genetic diversity of NS3 protease from Brazilian HCV isolates and possible implications for therapy with direct-acting antiviral drugs. Mem Inst Oswaldo Cruz, v.107, n.2, p.254-261, Mar. 2012.
dc.identifier.uri.fl_str_mv https://www.arca.fiocruz.br/handle/icict/16867
dc.identifier.issn.pt_BR.fl_str_mv 0074-0276
dc.identifier.eissn.none.fl_str_mv 1678-8060
identifier_str_mv SILVA, Allan Peres da; ALMEIDA, Adilson José de; LAMPE, Elisabeth. Genetic diversity of NS3 protease from Brazilian HCV isolates and possible implications for therapy with direct-acting antiviral drugs. Mem Inst Oswaldo Cruz, v.107, n.2, p.254-261, Mar. 2012.
0074-0276
1678-8060
url https://www.arca.fiocruz.br/handle/icict/16867
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 Fundação Oswaldo Cruz. Instituto Oswaldo Cruz
publisher.none.fl_str_mv Fundação Oswaldo Cruz. Instituto Oswaldo Cruz
dc.source.none.fl_str_mv reponame:Repositório Institucional da FIOCRUZ (ARCA)
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instacron:FIOCRUZ
instname_str Fundação Oswaldo Cruz (FIOCRUZ)
instacron_str FIOCRUZ
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collection Repositório Institucional da FIOCRUZ (ARCA)
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