Detection of lamivudine-resistant variants and mutations related to reduced antigenicity of HBsAg in individuals from the cities of Santos and São Paulo, Brazil
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 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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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 |
_version_ |
1822183981080117248 |
dc.identifier.doi.none.fl_str_mv |
10.1186/1743-422X-10-320 |