Detection of lamivudine-resistant variants and mutations related to reduced antigenicity of HBsAg in individuals from the cities of Santos and São Paulo, Brazil

Detalhes bibliográficos
Autor(a) principal: Mantovani, Nathalia [UNIFESP]
Data de Publicação: 2013
Outros Autores: Cicero, Maira [UNIFESP], Santana, Luiz Claudio [UNIFESP], Silveira, Carla, Carmo, Eliane Pereira do [UNIFESP], Abrao, Paulo Roberto Ferreira [UNIFESP], Diaz, Ricardo Sobhie [UNIFESP], Caseiro, Marcos Montani, Komninakis, Shirley Vasconcelos [UNIFESP]
Tipo de documento: Artigo
Idioma: eng
Título da fonte: Repositório Institucional da UNIFESP
dARK ID: ark:/48912/0013000018n40
DOI: 10.1186/1743-422X-10-320
Texto Completo: http://dx.doi.org/10.1186/1743-422X-10-320
http://repositorio.unifesp.br/handle/11600/36883
Resumo: Background: Continuous long-term treatment is recommended to reduce the hepatitis B virus (HBV) viral load. However, as a consequence, resistance mutations can emerge and be transmitted to other individuals. the polymerase (POL) gene overlaps the surface (S) gene. Thus, during treatment, mutations in the POL gene may lead to changes in hepatitis B surface antigen (HBsAg). the purpose of this study was to evaluate the frequency of lamivudine and vaccine escape mutations in HBsAg-positive blood donors from the city of Santos and in untreated HBV mono-infected patients from the city of São Paulo, Brazil.Methods: HBV DNA was extracted from 80 serum samples, of which 61 were from volunteer blood donors and 19 were from untreated HBV patients. A fragment of the POL/S genes containing 593 base pairs was amplified using nested PCR. Thirty four were PCR-positive and sequencing was performed using an ABI Prism 3130 Genetic Analyzer. Alignments and mutation mapping were performed using BioEdit software.Results: HBV DNA from 21 blood donors and 13 untreated patient samples were characterized using nucleotide sequencing PCR products from the POL/S genes. We were able to detect one sample with the resistance mutation to lamivudine rtM204V + rtL180M (2.94%), which was found in a volunteer blood donor that has never used antiviral drugs. the other samples showed only compensatory mutations, such as rtL80F (5.88%), rtL80V (2.94%), rtL82V + rtV207L (2.94%), rtT128P (5.88%), rtT128N/S (2.94%) and rtS219A (5.88%). We found modifications in the S gene in 14 of the 34 samples (41.16%). the mutations detected were as follows: sM133L + sI195T (2.94%), sI195M (2.94%), sP120T (2.94%), sY100S/F (2.94%), sY100C (17.64%), sI/T126P + sQ129P (2.94%), sM198I + sF183C (2.94%) and sS210R (5.88%).Conclusions: Our results suggest the transmission of lamivudine-resistant forms. Thus, the evaluation of HBV-infected subjects for lamivudine resistance would improve treatment regime. Moreover, the mutations in the S gene may impair HBsAg antigenicity and contribute to HBsAg failure detection and vaccine escape.
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spelling Detection of lamivudine-resistant variants and mutations related to reduced antigenicity of HBsAg in individuals from the cities of Santos and São Paulo, BrazilHBVGenotypesTransmitted drug resistanceLamivudineVaccine escape mutationsPolymerase geneSurface geneSurface antigenBackground: Continuous long-term treatment is recommended to reduce the hepatitis B virus (HBV) viral load. However, as a consequence, resistance mutations can emerge and be transmitted to other individuals. the polymerase (POL) gene overlaps the surface (S) gene. Thus, during treatment, mutations in the POL gene may lead to changes in hepatitis B surface antigen (HBsAg). the purpose of this study was to evaluate the frequency of lamivudine and vaccine escape mutations in HBsAg-positive blood donors from the city of Santos and in untreated HBV mono-infected patients from the city of São Paulo, Brazil.Methods: HBV DNA was extracted from 80 serum samples, of which 61 were from volunteer blood donors and 19 were from untreated HBV patients. A fragment of the POL/S genes containing 593 base pairs was amplified using nested PCR. Thirty four were PCR-positive and sequencing was performed using an ABI Prism 3130 Genetic Analyzer. Alignments and mutation mapping were performed using BioEdit software.Results: HBV DNA from 21 blood donors and 13 untreated patient samples were characterized using nucleotide sequencing PCR products from the POL/S genes. We were able to detect one sample with the resistance mutation to lamivudine rtM204V + rtL180M (2.94%), which was found in a volunteer blood donor that has never used antiviral drugs. the other samples showed only compensatory mutations, such as rtL80F (5.88%), rtL80V (2.94%), rtL82V + rtV207L (2.94%), rtT128P (5.88%), rtT128N/S (2.94%) and rtS219A (5.88%). We found modifications in the S gene in 14 of the 34 samples (41.16%). the mutations detected were as follows: sM133L + sI195T (2.94%), sI195M (2.94%), sP120T (2.94%), sY100S/F (2.94%), sY100C (17.64%), sI/T126P + sQ129P (2.94%), sM198I + sF183C (2.94%) and sS210R (5.88%).Conclusions: Our results suggest the transmission of lamivudine-resistant forms. Thus, the evaluation of HBV-infected subjects for lamivudine resistance would improve treatment regime. Moreover, the mutations in the S gene may impair HBsAg antigenicity and contribute to HBsAg failure detection and vaccine escape.Universidade Federal de São Paulo, Retrovirol Lab, Div Infect Dis, BR-04039032 São Paulo, BrazilLusiada Fdn, Mol Biol Lab, Dept Med, Santos, BrazilUniversidade Federal de São Paulo, Ambulatory Ctr Control Immune Deficiencies, BR-04039032 São Paulo, BrazilUniversidade Federal de São Paulo, Retrovirol Lab, Div Infect Dis, BR-04039032 São Paulo, BrazilUniversidade Federal de São Paulo, Ambulatory Ctr Control Immune Deficiencies, BR-04039032 São Paulo, BrazilWeb of ScienceBiomed Central LtdUniversidade Federal de São Paulo (UNIFESP)Lusiada FdnMantovani, Nathalia [UNIFESP]Cicero, Maira [UNIFESP]Santana, Luiz Claudio [UNIFESP]Silveira, CarlaCarmo, Eliane Pereira do [UNIFESP]Abrao, Paulo Roberto Ferreira [UNIFESP]Diaz, Ricardo Sobhie [UNIFESP]Caseiro, Marcos MontaniKomninakis, Shirley Vasconcelos [UNIFESP]2016-01-24T14:34:35Z2016-01-24T14:34:35Z2013-10-28info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersion5application/pdfhttp://dx.doi.org/10.1186/1743-422X-10-320Virology Journal. London: Biomed Central Ltd, v. 10, 5 p., 2013.10.1186/1743-422X-10-320WOS000332380600001.pdf1743-422Xhttp://repositorio.unifesp.br/handle/11600/36883WOS:000332380600001ark:/48912/0013000018n40engVirology Journalinfo:eu-repo/semantics/openAccessreponame:Repositório Institucional da UNIFESPinstname:Universidade Federal de São Paulo (UNIFESP)instacron:UNIFESP2024-10-14T10:59:59Zoai:repositorio.unifesp.br/:11600/36883Repositório InstitucionalPUBhttp://www.repositorio.unifesp.br/oai/requestbiblioteca.csp@unifesp.bropendoar:34652024-12-11T21:03:56.236638Repositório Institucional da UNIFESP - Universidade Federal de São Paulo (UNIFESP)false
dc.title.none.fl_str_mv Detection of lamivudine-resistant variants and mutations related to reduced antigenicity of HBsAg in individuals from the cities of Santos and São Paulo, Brazil
title Detection of lamivudine-resistant variants and mutations related to reduced antigenicity of HBsAg in individuals from the cities of Santos and São Paulo, Brazil
spellingShingle Detection of lamivudine-resistant variants and mutations related to reduced antigenicity of HBsAg in individuals from the cities of Santos and São Paulo, Brazil
Detection of lamivudine-resistant variants and mutations related to reduced antigenicity of HBsAg in individuals from the cities of Santos and São Paulo, Brazil
Mantovani, Nathalia [UNIFESP]
HBV
Genotypes
Transmitted drug resistance
Lamivudine
Vaccine escape mutations
Polymerase gene
Surface gene
Surface antigen
Mantovani, Nathalia [UNIFESP]
HBV
Genotypes
Transmitted drug resistance
Lamivudine
Vaccine escape mutations
Polymerase gene
Surface gene
Surface antigen
title_short Detection of lamivudine-resistant variants and mutations related to reduced antigenicity of HBsAg in individuals from the cities of Santos and São Paulo, Brazil
title_full Detection of lamivudine-resistant variants and mutations related to reduced antigenicity of HBsAg in individuals from the cities of Santos and São Paulo, Brazil
title_fullStr Detection of lamivudine-resistant variants and mutations related to reduced antigenicity of HBsAg in individuals from the cities of Santos and São Paulo, Brazil
Detection of lamivudine-resistant variants and mutations related to reduced antigenicity of HBsAg in individuals from the cities of Santos and São Paulo, Brazil
title_full_unstemmed Detection of lamivudine-resistant variants and mutations related to reduced antigenicity of HBsAg in individuals from the cities of Santos and São Paulo, Brazil
Detection of lamivudine-resistant variants and mutations related to reduced antigenicity of HBsAg in individuals from the cities of Santos and São Paulo, Brazil
title_sort Detection of lamivudine-resistant variants and mutations related to reduced antigenicity of HBsAg in individuals from the cities of Santos and São Paulo, Brazil
author Mantovani, Nathalia [UNIFESP]
author_facet Mantovani, Nathalia [UNIFESP]
Mantovani, Nathalia [UNIFESP]
Cicero, Maira [UNIFESP]
Santana, Luiz Claudio [UNIFESP]
Silveira, Carla
Carmo, Eliane Pereira do [UNIFESP]
Abrao, Paulo Roberto Ferreira [UNIFESP]
Diaz, Ricardo Sobhie [UNIFESP]
Caseiro, Marcos Montani
Komninakis, Shirley Vasconcelos [UNIFESP]
Cicero, Maira [UNIFESP]
Santana, Luiz Claudio [UNIFESP]
Silveira, Carla
Carmo, Eliane Pereira do [UNIFESP]
Abrao, Paulo Roberto Ferreira [UNIFESP]
Diaz, Ricardo Sobhie [UNIFESP]
Caseiro, Marcos Montani
Komninakis, Shirley Vasconcelos [UNIFESP]
author_role author
author2 Cicero, Maira [UNIFESP]
Santana, Luiz Claudio [UNIFESP]
Silveira, Carla
Carmo, Eliane Pereira do [UNIFESP]
Abrao, Paulo Roberto Ferreira [UNIFESP]
Diaz, Ricardo Sobhie [UNIFESP]
Caseiro, Marcos Montani
Komninakis, Shirley Vasconcelos [UNIFESP]
author2_role author
author
author
author
author
author
author
author
dc.contributor.none.fl_str_mv Universidade Federal de São Paulo (UNIFESP)
Lusiada Fdn
dc.contributor.author.fl_str_mv Mantovani, Nathalia [UNIFESP]
Cicero, Maira [UNIFESP]
Santana, Luiz Claudio [UNIFESP]
Silveira, Carla
Carmo, Eliane Pereira do [UNIFESP]
Abrao, Paulo Roberto Ferreira [UNIFESP]
Diaz, Ricardo Sobhie [UNIFESP]
Caseiro, Marcos Montani
Komninakis, Shirley Vasconcelos [UNIFESP]
dc.subject.por.fl_str_mv HBV
Genotypes
Transmitted drug resistance
Lamivudine
Vaccine escape mutations
Polymerase gene
Surface gene
Surface antigen
topic HBV
Genotypes
Transmitted drug resistance
Lamivudine
Vaccine escape mutations
Polymerase gene
Surface gene
Surface antigen
description Background: Continuous long-term treatment is recommended to reduce the hepatitis B virus (HBV) viral load. However, as a consequence, resistance mutations can emerge and be transmitted to other individuals. the polymerase (POL) gene overlaps the surface (S) gene. Thus, during treatment, mutations in the POL gene may lead to changes in hepatitis B surface antigen (HBsAg). the purpose of this study was to evaluate the frequency of lamivudine and vaccine escape mutations in HBsAg-positive blood donors from the city of Santos and in untreated HBV mono-infected patients from the city of São Paulo, Brazil.Methods: HBV DNA was extracted from 80 serum samples, of which 61 were from volunteer blood donors and 19 were from untreated HBV patients. A fragment of the POL/S genes containing 593 base pairs was amplified using nested PCR. Thirty four were PCR-positive and sequencing was performed using an ABI Prism 3130 Genetic Analyzer. Alignments and mutation mapping were performed using BioEdit software.Results: HBV DNA from 21 blood donors and 13 untreated patient samples were characterized using nucleotide sequencing PCR products from the POL/S genes. We were able to detect one sample with the resistance mutation to lamivudine rtM204V + rtL180M (2.94%), which was found in a volunteer blood donor that has never used antiviral drugs. the other samples showed only compensatory mutations, such as rtL80F (5.88%), rtL80V (2.94%), rtL82V + rtV207L (2.94%), rtT128P (5.88%), rtT128N/S (2.94%) and rtS219A (5.88%). We found modifications in the S gene in 14 of the 34 samples (41.16%). the mutations detected were as follows: sM133L + sI195T (2.94%), sI195M (2.94%), sP120T (2.94%), sY100S/F (2.94%), sY100C (17.64%), sI/T126P + sQ129P (2.94%), sM198I + sF183C (2.94%) and sS210R (5.88%).Conclusions: Our results suggest the transmission of lamivudine-resistant forms. Thus, the evaluation of HBV-infected subjects for lamivudine resistance would improve treatment regime. Moreover, the mutations in the S gene may impair HBsAg antigenicity and contribute to HBsAg failure detection and vaccine escape.
publishDate 2013
dc.date.none.fl_str_mv 2013-10-28
2016-01-24T14:34:35Z
2016-01-24T14:34:35Z
dc.type.driver.fl_str_mv info:eu-repo/semantics/article
dc.type.status.fl_str_mv info:eu-repo/semantics/publishedVersion
format article
status_str publishedVersion
dc.identifier.uri.fl_str_mv http://dx.doi.org/10.1186/1743-422X-10-320
Virology Journal. London: Biomed Central Ltd, v. 10, 5 p., 2013.
10.1186/1743-422X-10-320
WOS000332380600001.pdf
1743-422X
http://repositorio.unifesp.br/handle/11600/36883
WOS:000332380600001
dc.identifier.dark.fl_str_mv ark:/48912/0013000018n40
url http://dx.doi.org/10.1186/1743-422X-10-320
http://repositorio.unifesp.br/handle/11600/36883
identifier_str_mv Virology Journal. London: Biomed Central Ltd, v. 10, 5 p., 2013.
10.1186/1743-422X-10-320
WOS000332380600001.pdf
1743-422X
WOS:000332380600001
ark:/48912/0013000018n40
dc.language.iso.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv Virology Journal
dc.rights.driver.fl_str_mv info:eu-repo/semantics/openAccess
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv 5
application/pdf
dc.publisher.none.fl_str_mv Biomed Central Ltd
publisher.none.fl_str_mv Biomed Central Ltd
dc.source.none.fl_str_mv reponame:Repositório Institucional da UNIFESP
instname:Universidade Federal de São Paulo (UNIFESP)
instacron:UNIFESP
instname_str Universidade Federal de São Paulo (UNIFESP)
instacron_str UNIFESP
institution UNIFESP
reponame_str Repositório Institucional da UNIFESP
collection Repositório Institucional da UNIFESP
repository.name.fl_str_mv Repositório Institucional da UNIFESP - Universidade Federal de São Paulo (UNIFESP)
repository.mail.fl_str_mv biblioteca.csp@unifesp.br
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dc.identifier.doi.none.fl_str_mv 10.1186/1743-422X-10-320