Analysis of HCV quasispecies dynamic under selective pressure of combined therapy
Autor(a) principal: | |
---|---|
Data de Publicação: | 2013 |
Outros Autores: | , , , , , , , , |
Tipo de documento: | Artigo |
Idioma: | eng |
Título da fonte: | Repositório Institucional da UNIFESP |
Texto Completo: | http://repositorio.unifesp.br/handle/11600/35898 http://dx.doi.org/10.1186/1471-2334-13-61 |
Resumo: | Background: the quasispecies composition of Hepatitis C virus (HCV) could have important implications with regard to viral persistence and response to interferon-based therapy. the complete NS5A was analyzed to evaluate whether the composition of NS5A quasispecies of HCV 1a/1b is related to responsiveness to combined interferon pegylated (PEG-IFN) and ribavirin therapy.Methods: Viral RNA was isolated from serum samples collected before, during and after treatment from virological sustained responder (SVR), non-responder (NR) and the end-of-treatment responder patients (ETR). NS5A region was amplified, cloned and sequenced. Six hundred and ninety full-length NS5A sequences were analyzed.Results: This study provides evidence that lower nucleotide diversity of the NS5A region pre-therapy is associated with viral clearance. Analysis of samples of NRs and the ETRs time points showed that genetic diversity of populations tend to decrease over time. Post-therapy population of ETRs presented higher genetic distance from baseline probably due to the bottleneck phenomenon observed for those patients in the end of treatment. the viral effective population of those patients also showed a strong decrease after therapy. Otherwise, NRs demonstrated a continuous variation or stability of effective populations and genetic diversity over time that did not seem to be related to therapy. Phylogenetic relationships concerning complete NS5A sequences obtained from patients did not demonstrate clustering associated with specific response patterns. However, distinctive clustering of pre/post-therapy sequences was observed. in addition, the evolution of quasispecies over time was subjected to purifying or relaxed purifying selection. Codons 157 (P03), 182 and 440 (P42), 62 and 404 (P44) were found to be under positive selective pressure but it failed to be related to the therapy.Conclusion: These results confirm the hypothesis that a relationship exists between NS5A heterogeneity and response to therapy in patients infected with chronic hepatitis C. |
id |
UFSP_91ac99943cccd7405c41a0c29e7876b4 |
---|---|
oai_identifier_str |
oai:repositorio.unifesp.br:11600/35898 |
network_acronym_str |
UFSP |
network_name_str |
Repositório Institucional da UNIFESP |
repository_id_str |
3465 |
spelling |
Jardim, Ana C. G.Bittar, CintiaMatos, Renata P. A.Yamasaki, Lilian H. T.Silva, Rafael A. [UNIFESP]Pinho, Joao R. R.Fachini, Roberta M.Carareto, Claudia M. A.Mello, Isabel Maria Vicente Guedes de Carvalho [UNIFESP]Rahal, PaulaSão Paulo State UnivUniversidade Federal de São Paulo (UNIFESP)Universidade de São Paulo (USP)Sao Jose do Rio Preto Sch Med2016-01-24T14:31:09Z2016-01-24T14:31:09Z2013-02-01Bmc Infectious Diseases. London: Biomed Central Ltd, v. 13, 16 p., 2013.1471-2334http://repositorio.unifesp.br/handle/11600/35898http://dx.doi.org/10.1186/1471-2334-13-61WOS000315901300001.pdf10.1186/1471-2334-13-61WOS:000315901300001Background: the quasispecies composition of Hepatitis C virus (HCV) could have important implications with regard to viral persistence and response to interferon-based therapy. the complete NS5A was analyzed to evaluate whether the composition of NS5A quasispecies of HCV 1a/1b is related to responsiveness to combined interferon pegylated (PEG-IFN) and ribavirin therapy.Methods: Viral RNA was isolated from serum samples collected before, during and after treatment from virological sustained responder (SVR), non-responder (NR) and the end-of-treatment responder patients (ETR). NS5A region was amplified, cloned and sequenced. Six hundred and ninety full-length NS5A sequences were analyzed.Results: This study provides evidence that lower nucleotide diversity of the NS5A region pre-therapy is associated with viral clearance. Analysis of samples of NRs and the ETRs time points showed that genetic diversity of populations tend to decrease over time. Post-therapy population of ETRs presented higher genetic distance from baseline probably due to the bottleneck phenomenon observed for those patients in the end of treatment. the viral effective population of those patients also showed a strong decrease after therapy. Otherwise, NRs demonstrated a continuous variation or stability of effective populations and genetic diversity over time that did not seem to be related to therapy. Phylogenetic relationships concerning complete NS5A sequences obtained from patients did not demonstrate clustering associated with specific response patterns. However, distinctive clustering of pre/post-therapy sequences was observed. in addition, the evolution of quasispecies over time was subjected to purifying or relaxed purifying selection. Codons 157 (P03), 182 and 440 (P42), 62 and 404 (P44) were found to be under positive selective pressure but it failed to be related to the therapy.Conclusion: These results confirm the hypothesis that a relationship exists between NS5A heterogeneity and response to therapy in patients infected with chronic hepatitis C.Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)São Paulo State Univ, Dept Biol, Inst Biosci Language & Exact Sci, Sao Jose Do Rio Preto, SP, BrazilUniversidade Federal de São Paulo, Div Gastroenterol, Lab Appl Mol Hepatol, Hepatitis Sect, São Paulo, BrazilUniv São Paulo, Sch Med, Dept Gastroenterol, São Paulo Inst Trop Med, São Paulo, BrazilSao Jose do Rio Preto Sch Med, Dept Hepatol, São Paulo, BrazilUniversidade Federal de São Paulo, Div Gastroenterol, Lab Appl Mol Hepatol, Hepatitis Sect, São Paulo, BrazilFAPESP: 07/52073-0FAPESP: 06/60012-9Web of Science16engBiomed Central LtdBmc Infectious DiseasesAnalysis of HCV quasispecies dynamic under selective pressure of combined therapyinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleinfo:eu-repo/semantics/openAccessreponame:Repositório Institucional da UNIFESPinstname:Universidade Federal de São Paulo (UNIFESP)instacron:UNIFESPORIGINALWOS000315901300001.pdfapplication/pdf2209338${dspace.ui.url}/bitstream/11600/35898/1/WOS000315901300001.pdf3f5f2e96c3c32667efc642546b1df92cMD51open accessTEXTWOS000315901300001.pdf.txtWOS000315901300001.pdf.txtExtracted texttext/plain69726${dspace.ui.url}/bitstream/11600/35898/2/WOS000315901300001.pdf.txt87df0d937dbb4d3b630998aa7df7417bMD52open access11600/358982022-09-27 10:00:02.376open accessoai:repositorio.unifesp.br:11600/35898Repositório InstitucionalPUBhttp://www.repositorio.unifesp.br/oai/requestopendoar:34652022-09-27T13:00:02Repositório Institucional da UNIFESP - Universidade Federal de São Paulo (UNIFESP)false |
dc.title.en.fl_str_mv |
Analysis of HCV quasispecies dynamic under selective pressure of combined therapy |
title |
Analysis of HCV quasispecies dynamic under selective pressure of combined therapy |
spellingShingle |
Analysis of HCV quasispecies dynamic under selective pressure of combined therapy Jardim, Ana C. G. |
title_short |
Analysis of HCV quasispecies dynamic under selective pressure of combined therapy |
title_full |
Analysis of HCV quasispecies dynamic under selective pressure of combined therapy |
title_fullStr |
Analysis of HCV quasispecies dynamic under selective pressure of combined therapy |
title_full_unstemmed |
Analysis of HCV quasispecies dynamic under selective pressure of combined therapy |
title_sort |
Analysis of HCV quasispecies dynamic under selective pressure of combined therapy |
author |
Jardim, Ana C. G. |
author_facet |
Jardim, Ana C. G. Bittar, Cintia Matos, Renata P. A. Yamasaki, Lilian H. T. Silva, Rafael A. [UNIFESP] Pinho, Joao R. R. Fachini, Roberta M. Carareto, Claudia M. A. Mello, Isabel Maria Vicente Guedes de Carvalho [UNIFESP] Rahal, Paula |
author_role |
author |
author2 |
Bittar, Cintia Matos, Renata P. A. Yamasaki, Lilian H. T. Silva, Rafael A. [UNIFESP] Pinho, Joao R. R. Fachini, Roberta M. Carareto, Claudia M. A. Mello, Isabel Maria Vicente Guedes de Carvalho [UNIFESP] Rahal, Paula |
author2_role |
author author author author author author author author author |
dc.contributor.institution.none.fl_str_mv |
São Paulo State Univ Universidade Federal de São Paulo (UNIFESP) Universidade de São Paulo (USP) Sao Jose do Rio Preto Sch Med |
dc.contributor.author.fl_str_mv |
Jardim, Ana C. G. Bittar, Cintia Matos, Renata P. A. Yamasaki, Lilian H. T. Silva, Rafael A. [UNIFESP] Pinho, Joao R. R. Fachini, Roberta M. Carareto, Claudia M. A. Mello, Isabel Maria Vicente Guedes de Carvalho [UNIFESP] Rahal, Paula |
description |
Background: the quasispecies composition of Hepatitis C virus (HCV) could have important implications with regard to viral persistence and response to interferon-based therapy. the complete NS5A was analyzed to evaluate whether the composition of NS5A quasispecies of HCV 1a/1b is related to responsiveness to combined interferon pegylated (PEG-IFN) and ribavirin therapy.Methods: Viral RNA was isolated from serum samples collected before, during and after treatment from virological sustained responder (SVR), non-responder (NR) and the end-of-treatment responder patients (ETR). NS5A region was amplified, cloned and sequenced. Six hundred and ninety full-length NS5A sequences were analyzed.Results: This study provides evidence that lower nucleotide diversity of the NS5A region pre-therapy is associated with viral clearance. Analysis of samples of NRs and the ETRs time points showed that genetic diversity of populations tend to decrease over time. Post-therapy population of ETRs presented higher genetic distance from baseline probably due to the bottleneck phenomenon observed for those patients in the end of treatment. the viral effective population of those patients also showed a strong decrease after therapy. Otherwise, NRs demonstrated a continuous variation or stability of effective populations and genetic diversity over time that did not seem to be related to therapy. Phylogenetic relationships concerning complete NS5A sequences obtained from patients did not demonstrate clustering associated with specific response patterns. However, distinctive clustering of pre/post-therapy sequences was observed. in addition, the evolution of quasispecies over time was subjected to purifying or relaxed purifying selection. Codons 157 (P03), 182 and 440 (P42), 62 and 404 (P44) were found to be under positive selective pressure but it failed to be related to the therapy.Conclusion: These results confirm the hypothesis that a relationship exists between NS5A heterogeneity and response to therapy in patients infected with chronic hepatitis C. |
publishDate |
2013 |
dc.date.issued.fl_str_mv |
2013-02-01 |
dc.date.accessioned.fl_str_mv |
2016-01-24T14:31:09Z |
dc.date.available.fl_str_mv |
2016-01-24T14:31:09Z |
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 |
Bmc Infectious Diseases. London: Biomed Central Ltd, v. 13, 16 p., 2013. |
dc.identifier.uri.fl_str_mv |
http://repositorio.unifesp.br/handle/11600/35898 http://dx.doi.org/10.1186/1471-2334-13-61 |
dc.identifier.issn.none.fl_str_mv |
1471-2334 |
dc.identifier.file.none.fl_str_mv |
WOS000315901300001.pdf |
dc.identifier.doi.none.fl_str_mv |
10.1186/1471-2334-13-61 |
dc.identifier.wos.none.fl_str_mv |
WOS:000315901300001 |
identifier_str_mv |
Bmc Infectious Diseases. London: Biomed Central Ltd, v. 13, 16 p., 2013. 1471-2334 WOS000315901300001.pdf 10.1186/1471-2334-13-61 WOS:000315901300001 |
url |
http://repositorio.unifesp.br/handle/11600/35898 http://dx.doi.org/10.1186/1471-2334-13-61 |
dc.language.iso.fl_str_mv |
eng |
language |
eng |
dc.relation.ispartof.none.fl_str_mv |
Bmc Infectious Diseases |
dc.rights.driver.fl_str_mv |
info:eu-repo/semantics/openAccess |
eu_rights_str_mv |
openAccess |
dc.format.none.fl_str_mv |
16 |
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 |
bitstream.url.fl_str_mv |
${dspace.ui.url}/bitstream/11600/35898/1/WOS000315901300001.pdf ${dspace.ui.url}/bitstream/11600/35898/2/WOS000315901300001.pdf.txt |
bitstream.checksum.fl_str_mv |
3f5f2e96c3c32667efc642546b1df92c 87df0d937dbb4d3b630998aa7df7417b |
bitstream.checksumAlgorithm.fl_str_mv |
MD5 MD5 |
repository.name.fl_str_mv |
Repositório Institucional da UNIFESP - Universidade Federal de São Paulo (UNIFESP) |
repository.mail.fl_str_mv |
|
_version_ |
1802764166168051712 |