On Hepatitis C Virus Evolution: The Interaction between Virus and Host towards Treatment Outcome

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dc.contributor.authorBittar, Cíntia [UNESP]
dc.contributor.authorJardim, Ana Carolina Gomes [UNESP]
dc.contributor.authorYamasaki, Lilian Hiromi Tomonari [UNESP]
dc.contributor.authorCarareto, Claudia Márcia Aparecida [UNESP]
dc.contributor.authorPinho, João Renato Rebello
dc.contributor.authorLemey, Philippe
dc.contributor.authorde Carvalho-Mello, Isabel Maria Vicente Guedes
dc.contributor.authorRahal, Paula [UNESP]
dc.contributor.institutionUniversidade Estadual Paulista (Unesp)
dc.contributor.institutionUniversidade de São Paulo (USP)
dc.contributor.institutionAlbert Einstein Israeli Hospital
dc.contributor.institutionKatholieke Universiteit Leuven - Lab. of Clinical and Epidemiological Virology (Rega Institute)
dc.contributor.institutionUniversidade Federal de São Paulo (UNIFESP)
dc.date.accessioned2014-05-27T11:29:00Z
dc.date.available2014-05-27T11:29:00Z
dc.date.issued2013-04-25
dc.description.abstractBackground: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.en
dc.description.affiliationDepartment of Biology UNESP - São Paulo State University - IBILCE- - Institute of Bioscience Language and Literature and Exact Science, São José do Rio Preto, São Paulo
dc.description.affiliationDepartment of Gastroenterology - Laboratory of Hepatology and Gastroenterology Institute of Tropical Medicine USP - São Paulo University - Faculty of Medicine, São Paulo, São Paulo
dc.description.affiliationDepartment of Clinical Pathology Albert Einstein Israeli Hospital, São Paulo, São Paulo
dc.description.affiliationKatholieke Universiteit Leuven - Lab. of Clinical and Epidemiological Virology (Rega Institute), Leuven
dc.description.affiliationDepartamento de Medicina - Disciplina de Gastroenterologia Laboratório de Hepatologia Molecular Aplicada Universidade Federal de São Paulo - Escola Paulista de Medicina, São Paulo, São Paulo
dc.description.affiliationUnespDepartment of Biology UNESP - São Paulo State University - IBILCE- - Institute of Bioscience Language and Literature and Exact Science, São José do Rio Preto, São Paulo
dc.identifierhttp://dx.doi.org/10.1371/journal.pone.0062393
dc.identifier.citationPLoS ONE, v. 8, n. 4, 2013.
dc.identifier.doi10.1371/journal.pone.0062393
dc.identifier.file2-s2.0-84876704094.pdf
dc.identifier.issn1932-6203
dc.identifier.lattes7991082362671212
dc.identifier.lattes3425772998319216
dc.identifier.orcid0000-0001-5693-6148
dc.identifier.orcid0000-0002-0298-1354
dc.identifier.scopus2-s2.0-84876704094
dc.identifier.urihttp://hdl.handle.net/11449/75169
dc.identifier.wosWOS:000318341400053
dc.language.isoeng
dc.relation.ispartofPLOS ONE
dc.relation.ispartofjcr2.766
dc.relation.ispartofsjr1,164
dc.rights.accessRightsAcesso aberto
dc.sourceScopus
dc.subjectcomplementary DNA
dc.subjectnonstructural protein 5A
dc.subjectvirus RNA
dc.subjectcontrolled study
dc.subjectgenetic distance
dc.subjectgenetic selection
dc.subjectgenetic variability
dc.subjectgenotyping technique
dc.subjectHepatitis C virus
dc.subjecthuman
dc.subjectmicrobial population dynamics
dc.subjectmolecular evolution
dc.subjectmolecular phylogeny
dc.subjectnonhuman
dc.subjectnucleotide sequence
dc.subjectpopulation structure
dc.subjectRNA sequence
dc.subjectsequence analysis
dc.subjectstop codon
dc.subjectunindexed sequence
dc.subjectvirus cell interaction
dc.subjectvirus genome
dc.titleOn Hepatitis C Virus Evolution: The Interaction between Virus and Host towards Treatment Outcomeen
dc.typeArtigo
dcterms.licensehttp://www.plos.org/open-access/
unesp.author.lattes7991082362671212[8]
unesp.author.lattes3425772998319216[4]
unesp.author.orcid0000-0001-5693-6148[8]
unesp.author.orcid0000-0002-0298-1354[4]
unesp.campusUniversidade Estadual Paulista (Unesp), Instituto de Biociências Letras e Ciências Exatas, São José do Rio Pretopt

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