On Hepatitis C Virus Evolution: The Interaction between Virus and Host towards Treatment Outcome
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 UNESP |
Texto Completo: | http://dx.doi.org/10.1371/journal.pone.0062393 http://hdl.handle.net/11449/75169 |
Resumo: | Background:Hepatitis C is a disease spread throughout the world. Hepatitis C virus (HCV), the etiological agent of this disease, is a single-stranded positive RNA virus. Its genome encodes a single precursor protein that yields ten proteins after processing. NS5A, one of the non-structural viral proteins, is most associated with interferon-based therapy response, the approved treatment for hepatitis C in Brazil. HCV has a high mutation rate and therefore high variability, which may be important for evading the immune system and response to therapy. The aim of this study was to analyze the evolution of NS5A quasispecies before, during, and after treatment in patients infected with HCV genotype 3a who presented different therapy responses.Methods:Viral RNA was extracted, cDNA was synthesized, the NS5A region was amplified and cloned, and 15 clones from each time-point were sequenced. The sequences were analyzed for evolutionary history, genetic diversity and selection.Results:This analysis shows that the viral population that persists after treatment for most non-responder patients is present in before-treatment samples, suggesting it is adapted to evade treatment. In contrast, the population found in before treatment samples from most end-of-treatment responder patients either are selected out or appears in low frequency after relapse, therefore changing the population structure. The exceptions illustrate the uniqueness of the evolutionary process, and therefore the treatment resistance process, in each patient.Conclusion:Although evolutionary behavior throughout treatment showed that each patient presented different population dynamics unrelated to therapy outcome, it seems that the viral population from non-responders that resists the treatment already had strains that could evade therapy before it started. © 2013 Bittar et al. |
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On Hepatitis C Virus Evolution: The Interaction between Virus and Host towards Treatment Outcomecomplementary DNAnonstructural protein 5Avirus RNAcontrolled studygenetic distancegenetic selectiongenetic variabilitygenotyping techniqueHepatitis C virushumanmicrobial population dynamicsmolecular evolutionmolecular phylogenynonhumannucleotide sequencepopulation structureRNA sequencesequence analysisstop codonunindexed sequencevirus cell interactionvirus genomeBackground:Hepatitis C is a disease spread throughout the world. Hepatitis C virus (HCV), the etiological agent of this disease, is a single-stranded positive RNA virus. Its genome encodes a single precursor protein that yields ten proteins after processing. NS5A, one of the non-structural viral proteins, is most associated with interferon-based therapy response, the approved treatment for hepatitis C in Brazil. HCV has a high mutation rate and therefore high variability, which may be important for evading the immune system and response to therapy. The aim of this study was to analyze the evolution of NS5A quasispecies before, during, and after treatment in patients infected with HCV genotype 3a who presented different therapy responses.Methods:Viral RNA was extracted, cDNA was synthesized, the NS5A region was amplified and cloned, and 15 clones from each time-point were sequenced. The sequences were analyzed for evolutionary history, genetic diversity and selection.Results:This analysis shows that the viral population that persists after treatment for most non-responder patients is present in before-treatment samples, suggesting it is adapted to evade treatment. In contrast, the population found in before treatment samples from most end-of-treatment responder patients either are selected out or appears in low frequency after relapse, therefore changing the population structure. The exceptions illustrate the uniqueness of the evolutionary process, and therefore the treatment resistance process, in each patient.Conclusion:Although evolutionary behavior throughout treatment showed that each patient presented different population dynamics unrelated to therapy outcome, it seems that the viral population from non-responders that resists the treatment already had strains that could evade therapy before it started. © 2013 Bittar et al.Department of Biology UNESP - São Paulo State University - IBILCE- - Institute of Bioscience Language and Literature and Exact Science, São José do Rio Preto, São PauloDepartment of Gastroenterology - Laboratory of Hepatology and Gastroenterology Institute of Tropical Medicine USP - São Paulo University - Faculty of Medicine, São Paulo, São PauloDepartment of Clinical Pathology Albert Einstein Israeli Hospital, São Paulo, São PauloKatholieke Universiteit Leuven - Lab. of Clinical and Epidemiological Virology (Rega Institute), LeuvenDepartamento de Medicina - Disciplina de Gastroenterologia Laboratório de Hepatologia Molecular Aplicada Universidade Federal de São Paulo - Escola Paulista de Medicina, São Paulo, São PauloDepartment of Biology UNESP - São Paulo State University - IBILCE- - Institute of Bioscience Language and Literature and Exact Science, São José do Rio Preto, São PauloUniversidade Estadual Paulista (Unesp)Universidade de São Paulo (USP)Albert Einstein Israeli HospitalKatholieke Universiteit Leuven - Lab. of Clinical and Epidemiological Virology (Rega Institute)Universidade Federal de São Paulo (UNIFESP)Bittar, Cíntia [UNESP]Jardim, Ana Carolina Gomes [UNESP]Yamasaki, Lilian Hiromi Tomonari [UNESP]Carareto, Claudia Márcia Aparecida [UNESP]Pinho, João Renato RebelloLemey, Philippede Carvalho-Mello, Isabel Maria Vicente GuedesRahal, Paula [UNESP]2014-05-27T11:29:00Z2014-05-27T11:29:00Z2013-04-25info:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleapplication/pdfhttp://dx.doi.org/10.1371/journal.pone.0062393PLoS ONE, v. 8, n. 4, 2013.1932-6203http://hdl.handle.net/11449/7516910.1371/journal.pone.0062393WOS:0003183414000532-s2.0-848767040942-s2.0-84876704094.pdf799108236267121234257729983192160000-0001-5693-61480000-0002-0298-1354Scopusreponame:Repositório Institucional da UNESPinstname:Universidade Estadual Paulista (UNESP)instacron:UNESPengPLOS ONE2.7661,164info:eu-repo/semantics/openAccess2023-12-26T06:16:59Zoai:repositorio.unesp.br:11449/75169Repositório InstitucionalPUBhttp://repositorio.unesp.br/oai/requestopendoar:29462024-08-05T21:19:51.413532Repositório Institucional da UNESP - Universidade Estadual Paulista (UNESP)false |
dc.title.none.fl_str_mv |
On Hepatitis C Virus Evolution: The Interaction between Virus and Host towards Treatment Outcome |
title |
On Hepatitis C Virus Evolution: The Interaction between Virus and Host towards Treatment Outcome |
spellingShingle |
On Hepatitis C Virus Evolution: The Interaction between Virus and Host towards Treatment Outcome Bittar, Cíntia [UNESP] complementary DNA nonstructural protein 5A virus RNA controlled study genetic distance genetic selection genetic variability genotyping technique Hepatitis C virus human microbial population dynamics molecular evolution molecular phylogeny nonhuman nucleotide sequence population structure RNA sequence sequence analysis stop codon unindexed sequence virus cell interaction virus genome |
title_short |
On Hepatitis C Virus Evolution: The Interaction between Virus and Host towards Treatment Outcome |
title_full |
On Hepatitis C Virus Evolution: The Interaction between Virus and Host towards Treatment Outcome |
title_fullStr |
On Hepatitis C Virus Evolution: The Interaction between Virus and Host towards Treatment Outcome |
title_full_unstemmed |
On Hepatitis C Virus Evolution: The Interaction between Virus and Host towards Treatment Outcome |
title_sort |
On Hepatitis C Virus Evolution: The Interaction between Virus and Host towards Treatment Outcome |
author |
Bittar, Cíntia [UNESP] |
author_facet |
Bittar, Cíntia [UNESP] Jardim, Ana Carolina Gomes [UNESP] Yamasaki, Lilian Hiromi Tomonari [UNESP] Carareto, Claudia Márcia Aparecida [UNESP] Pinho, João Renato Rebello Lemey, Philippe de Carvalho-Mello, Isabel Maria Vicente Guedes Rahal, Paula [UNESP] |
author_role |
author |
author2 |
Jardim, Ana Carolina Gomes [UNESP] Yamasaki, Lilian Hiromi Tomonari [UNESP] Carareto, Claudia Márcia Aparecida [UNESP] Pinho, João Renato Rebello Lemey, Philippe de Carvalho-Mello, Isabel Maria Vicente Guedes Rahal, Paula [UNESP] |
author2_role |
author author author author author author author |
dc.contributor.none.fl_str_mv |
Universidade Estadual Paulista (Unesp) Universidade de São Paulo (USP) Albert Einstein Israeli Hospital Katholieke Universiteit Leuven - Lab. of Clinical and Epidemiological Virology (Rega Institute) Universidade Federal de São Paulo (UNIFESP) |
dc.contributor.author.fl_str_mv |
Bittar, Cíntia [UNESP] Jardim, Ana Carolina Gomes [UNESP] Yamasaki, Lilian Hiromi Tomonari [UNESP] Carareto, Claudia Márcia Aparecida [UNESP] Pinho, João Renato Rebello Lemey, Philippe de Carvalho-Mello, Isabel Maria Vicente Guedes Rahal, Paula [UNESP] |
dc.subject.por.fl_str_mv |
complementary DNA nonstructural protein 5A virus RNA controlled study genetic distance genetic selection genetic variability genotyping technique Hepatitis C virus human microbial population dynamics molecular evolution molecular phylogeny nonhuman nucleotide sequence population structure RNA sequence sequence analysis stop codon unindexed sequence virus cell interaction virus genome |
topic |
complementary DNA nonstructural protein 5A virus RNA controlled study genetic distance genetic selection genetic variability genotyping technique Hepatitis C virus human microbial population dynamics molecular evolution molecular phylogeny nonhuman nucleotide sequence population structure RNA sequence sequence analysis stop codon unindexed sequence virus cell interaction virus genome |
description |
Background:Hepatitis C is a disease spread throughout the world. Hepatitis C virus (HCV), the etiological agent of this disease, is a single-stranded positive RNA virus. Its genome encodes a single precursor protein that yields ten proteins after processing. NS5A, one of the non-structural viral proteins, is most associated with interferon-based therapy response, the approved treatment for hepatitis C in Brazil. HCV has a high mutation rate and therefore high variability, which may be important for evading the immune system and response to therapy. The aim of this study was to analyze the evolution of NS5A quasispecies before, during, and after treatment in patients infected with HCV genotype 3a who presented different therapy responses.Methods:Viral RNA was extracted, cDNA was synthesized, the NS5A region was amplified and cloned, and 15 clones from each time-point were sequenced. The sequences were analyzed for evolutionary history, genetic diversity and selection.Results:This analysis shows that the viral population that persists after treatment for most non-responder patients is present in before-treatment samples, suggesting it is adapted to evade treatment. In contrast, the population found in before treatment samples from most end-of-treatment responder patients either are selected out or appears in low frequency after relapse, therefore changing the population structure. The exceptions illustrate the uniqueness of the evolutionary process, and therefore the treatment resistance process, in each patient.Conclusion:Although evolutionary behavior throughout treatment showed that each patient presented different population dynamics unrelated to therapy outcome, it seems that the viral population from non-responders that resists the treatment already had strains that could evade therapy before it started. © 2013 Bittar et al. |
publishDate |
2013 |
dc.date.none.fl_str_mv |
2013-04-25 2014-05-27T11:29:00Z 2014-05-27T11:29:00Z |
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/10.1371/journal.pone.0062393 PLoS ONE, v. 8, n. 4, 2013. 1932-6203 http://hdl.handle.net/11449/75169 10.1371/journal.pone.0062393 WOS:000318341400053 2-s2.0-84876704094 2-s2.0-84876704094.pdf 7991082362671212 3425772998319216 0000-0001-5693-6148 0000-0002-0298-1354 |
url |
http://dx.doi.org/10.1371/journal.pone.0062393 http://hdl.handle.net/11449/75169 |
identifier_str_mv |
PLoS ONE, v. 8, n. 4, 2013. 1932-6203 10.1371/journal.pone.0062393 WOS:000318341400053 2-s2.0-84876704094 2-s2.0-84876704094.pdf 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 |
PLOS ONE 2.766 1,164 |
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) |
repository.mail.fl_str_mv |
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1808129310301618176 |