Analysis of HCV quasispecies dynamic under selective pressure of combined therapy

Detalhes bibliográficos
Autor(a) principal: Jardim, Ana C.G. [UNESP]
Data de Publicação: 2013
Outros Autores: Bittar, Cíntia [UNESP], Matos, Renata P.A. [UNESP], Yamasaki, Lílian H.T. [UNESP], Silva, Rafael A., Pinho, João R.R., Fachini, Roberta M., Carareto, Claudia M.A. [UNESP], de Carvalho-Mello, Isabel M.V.G., Rahal, Paula [UNESP]
Tipo de documento: Artigo
Idioma: eng
Título da fonte: Repositório Institucional da UNESP
Texto Completo: http://dx.doi.org/10.1186/1471-2334-13-61
http://hdl.handle.net/11449/74529
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. © 2013 Jardim et al.; licensee BioMed Central Ltd.
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spelling Analysis of HCV quasispecies dynamic under selective pressure of combined therapynonstructural protein 5Apeginterferon alpha2bribavirinadultamino acid sequenceamino terminal sequencebottleneck populationcarboxy terminal sequencecladisticsclinical effectivenesscodoncombination chemotherapydrug responsefemalegenetic distancegenetic variabilityhepatitis CHepatitis C virushumanmajor clinical studymalemolecular phylogenynonhumannonsense mutationnucleotide sequencephylogenetic treepurifying selectionsequence alignmentsequence analysissex differenceviral clearanceviremiavirus loadBackground: 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. © 2013 Jardim et al.; licensee BioMed Central Ltd.Departament of Biology Institute of Bioscience, Language and Exact Science São Paulo State University, São José do Rio Preto, SPDivision of Gastroenterology Laboratory of Applied Molecular Hepatology Hepatitis Section Federal University of São Paulo, São Paulo, SPDepartament of Gastroenterology São Paulo Institute of Tropical Medicine School of Medicine, University of São Paulo, São Paulo, SPDepartment Hepatology São José do Rio Preto School of Medicine, São Paulo, SPDepartament of Biology Institute of Bioscience, Language and Exact Science São Paulo State University, São José do Rio Preto, SPUniversidade Estadual Paulista (Unesp)Universidade de São Paulo (USP)São José do Rio Preto School of MedicineJardim, Ana C.G. [UNESP]Bittar, Cíntia [UNESP]Matos, Renata P.A. [UNESP]Yamasaki, Lílian H.T. [UNESP]Silva, Rafael A.Pinho, João R.R.Fachini, Roberta M.Carareto, Claudia M.A. [UNESP]de Carvalho-Mello, Isabel M.V.G.Rahal, Paula [UNESP]2014-05-27T11:28:20Z2014-05-27T11:28:20Z2013-02-01info:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleapplication/pdfhttp://dx.doi.org/10.1186/1471-2334-13-61BMC Infectious Diseases, v. 13, n. 1, 2013.1471-2334http://hdl.handle.net/11449/7452910.1186/1471-2334-13-61WOS:0003159013000012-s2.0-848730464122-s2.0-84873046412.pdf9424175688206545799108236267121234257729983192160000-0001-5693-61480000-0002-0298-1354Scopusreponame:Repositório Institucional da UNESPinstname:Universidade Estadual Paulista (UNESP)instacron:UNESPengBMC Infectious Diseases2.6201,576info:eu-repo/semantics/openAccess2023-12-16T06:25:11Zoai:repositorio.unesp.br:11449/74529Repositório InstitucionalPUBhttp://repositorio.unesp.br/oai/requestopendoar:29462023-12-16T06:25:11Repositório Institucional da UNESP - Universidade Estadual Paulista (UNESP)false
dc.title.none.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. [UNESP]
nonstructural protein 5A
peginterferon alpha2b
ribavirin
adult
amino acid sequence
amino terminal sequence
bottleneck population
carboxy terminal sequence
cladistics
clinical effectiveness
codon
combination chemotherapy
drug response
female
genetic distance
genetic variability
hepatitis C
Hepatitis C virus
human
major clinical study
male
molecular phylogeny
nonhuman
nonsense mutation
nucleotide sequence
phylogenetic tree
purifying selection
sequence alignment
sequence analysis
sex difference
viral clearance
viremia
virus load
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. [UNESP]
author_facet Jardim, Ana C.G. [UNESP]
Bittar, Cíntia [UNESP]
Matos, Renata P.A. [UNESP]
Yamasaki, Lílian H.T. [UNESP]
Silva, Rafael A.
Pinho, João R.R.
Fachini, Roberta M.
Carareto, Claudia M.A. [UNESP]
de Carvalho-Mello, Isabel M.V.G.
Rahal, Paula [UNESP]
author_role author
author2 Bittar, Cíntia [UNESP]
Matos, Renata P.A. [UNESP]
Yamasaki, Lílian H.T. [UNESP]
Silva, Rafael A.
Pinho, João R.R.
Fachini, Roberta M.
Carareto, Claudia M.A. [UNESP]
de Carvalho-Mello, Isabel M.V.G.
Rahal, Paula [UNESP]
author2_role author
author
author
author
author
author
author
author
author
dc.contributor.none.fl_str_mv Universidade Estadual Paulista (Unesp)
Universidade de São Paulo (USP)
São José do Rio Preto School of Medicine
dc.contributor.author.fl_str_mv Jardim, Ana C.G. [UNESP]
Bittar, Cíntia [UNESP]
Matos, Renata P.A. [UNESP]
Yamasaki, Lílian H.T. [UNESP]
Silva, Rafael A.
Pinho, João R.R.
Fachini, Roberta M.
Carareto, Claudia M.A. [UNESP]
de Carvalho-Mello, Isabel M.V.G.
Rahal, Paula [UNESP]
dc.subject.por.fl_str_mv nonstructural protein 5A
peginterferon alpha2b
ribavirin
adult
amino acid sequence
amino terminal sequence
bottleneck population
carboxy terminal sequence
cladistics
clinical effectiveness
codon
combination chemotherapy
drug response
female
genetic distance
genetic variability
hepatitis C
Hepatitis C virus
human
major clinical study
male
molecular phylogeny
nonhuman
nonsense mutation
nucleotide sequence
phylogenetic tree
purifying selection
sequence alignment
sequence analysis
sex difference
viral clearance
viremia
virus load
topic nonstructural protein 5A
peginterferon alpha2b
ribavirin
adult
amino acid sequence
amino terminal sequence
bottleneck population
carboxy terminal sequence
cladistics
clinical effectiveness
codon
combination chemotherapy
drug response
female
genetic distance
genetic variability
hepatitis C
Hepatitis C virus
human
major clinical study
male
molecular phylogeny
nonhuman
nonsense mutation
nucleotide sequence
phylogenetic tree
purifying selection
sequence alignment
sequence analysis
sex difference
viral clearance
viremia
virus load
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. © 2013 Jardim et al.; licensee BioMed Central Ltd.
publishDate 2013
dc.date.none.fl_str_mv 2013-02-01
2014-05-27T11:28:20Z
2014-05-27T11:28:20Z
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.uri.fl_str_mv http://dx.doi.org/10.1186/1471-2334-13-61
BMC Infectious Diseases, v. 13, n. 1, 2013.
1471-2334
http://hdl.handle.net/11449/74529
10.1186/1471-2334-13-61
WOS:000315901300001
2-s2.0-84873046412
2-s2.0-84873046412.pdf
9424175688206545
7991082362671212
3425772998319216
0000-0001-5693-6148
0000-0002-0298-1354
url http://dx.doi.org/10.1186/1471-2334-13-61
http://hdl.handle.net/11449/74529
identifier_str_mv BMC Infectious Diseases, v. 13, n. 1, 2013.
1471-2334
10.1186/1471-2334-13-61
WOS:000315901300001
2-s2.0-84873046412
2-s2.0-84873046412.pdf
9424175688206545
7991082362671212
3425772998319216
0000-0001-5693-6148
0000-0002-0298-1354
dc.language.iso.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv BMC Infectious Diseases
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1,576
dc.rights.driver.fl_str_mv info:eu-repo/semantics/openAccess
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
dc.source.none.fl_str_mv Scopus
reponame:Repositório Institucional da UNESP
instname:Universidade Estadual Paulista (UNESP)
instacron:UNESP
instname_str Universidade Estadual Paulista (UNESP)
instacron_str UNESP
institution UNESP
reponame_str Repositório Institucional da UNESP
collection Repositório Institucional da UNESP
repository.name.fl_str_mv Repositório Institucional da UNESP - Universidade Estadual Paulista (UNESP)
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