Analysis of HCV quasispecies dynamic under selective pressure of combined therapy

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dc.contributor.authorJardim, Ana C.G. [UNESP]
dc.contributor.authorBittar, Cíntia [UNESP]
dc.contributor.authorMatos, Renata P.A. [UNESP]
dc.contributor.authorYamasaki, Lílian H.T. [UNESP]
dc.contributor.authorSilva, Rafael A.
dc.contributor.authorPinho, João R.R.
dc.contributor.authorFachini, Roberta M.
dc.contributor.authorCarareto, Claudia M.A. [UNESP]
dc.contributor.authorde Carvalho-Mello, Isabel M.V.G.
dc.contributor.authorRahal, Paula [UNESP]
dc.contributor.institutionUniversidade Estadual Paulista (Unesp)
dc.contributor.institutionUniversidade de São Paulo (USP)
dc.contributor.institutionSão José do Rio Preto School of Medicine
dc.date.accessioned2014-05-27T11:28:20Z
dc.date.available2014-05-27T11:28:20Z
dc.date.issued2013-02-01
dc.description.abstractBackground: 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.en
dc.description.affiliationDepartament of Biology Institute of Bioscience, Language and Exact Science São Paulo State University, São José do Rio Preto, SP
dc.description.affiliationDivision of Gastroenterology Laboratory of Applied Molecular Hepatology Hepatitis Section Federal University of São Paulo, São Paulo, SP
dc.description.affiliationDepartament of Gastroenterology São Paulo Institute of Tropical Medicine School of Medicine, University of São Paulo, São Paulo, SP
dc.description.affiliationDepartment Hepatology São José do Rio Preto School of Medicine, São Paulo, SP
dc.description.affiliationUnespDepartament of Biology Institute of Bioscience, Language and Exact Science São Paulo State University, São José do Rio Preto, SP
dc.identifierhttp://dx.doi.org/10.1186/1471-2334-13-61
dc.identifier.citationBMC Infectious Diseases, v. 13, n. 1, 2013.
dc.identifier.doi10.1186/1471-2334-13-61
dc.identifier.file2-s2.0-84873046412.pdf
dc.identifier.issn1471-2334
dc.identifier.lattes9424175688206545
dc.identifier.lattes7991082362671212
dc.identifier.lattes3425772998319216
dc.identifier.orcid0000-0001-5693-6148
dc.identifier.orcid0000-0002-0298-1354
dc.identifier.scopus2-s2.0-84873046412
dc.identifier.urihttp://hdl.handle.net/11449/74529
dc.identifier.wosWOS:000315901300001
dc.language.isoeng
dc.relation.ispartofBMC Infectious Diseases
dc.relation.ispartofjcr2.620
dc.relation.ispartofsjr1,576
dc.rights.accessRightsAcesso aberto
dc.sourceScopus
dc.subjectnonstructural protein 5A
dc.subjectpeginterferon alpha2b
dc.subjectribavirin
dc.subjectadult
dc.subjectamino acid sequence
dc.subjectamino terminal sequence
dc.subjectbottleneck population
dc.subjectcarboxy terminal sequence
dc.subjectcladistics
dc.subjectclinical effectiveness
dc.subjectcodon
dc.subjectcombination chemotherapy
dc.subjectdrug response
dc.subjectfemale
dc.subjectgenetic distance
dc.subjectgenetic variability
dc.subjecthepatitis C
dc.subjectHepatitis C virus
dc.subjecthuman
dc.subjectmajor clinical study
dc.subjectmale
dc.subjectmolecular phylogeny
dc.subjectnonhuman
dc.subjectnonsense mutation
dc.subjectnucleotide sequence
dc.subjectphylogenetic tree
dc.subjectpurifying selection
dc.subjectsequence alignment
dc.subjectsequence analysis
dc.subjectsex difference
dc.subjectviral clearance
dc.subjectviremia
dc.subjectvirus load
dc.titleAnalysis of HCV quasispecies dynamic under selective pressure of combined therapyen
dc.typeArtigo
dcterms.licensehttp://www.biomedcentral.com/about/license
unesp.author.lattes9424175688206545
unesp.author.lattes7991082362671212[10]
unesp.author.lattes3425772998319216[8]
unesp.author.orcid0000-0001-5693-6148[10]
unesp.author.orcid0000-0002-0298-1354[8]
unesp.campusUniversidade Estadual Paulista (Unesp), Instituto de Biociências Letras e Ciências Exatas, São José do Rio Pretopt

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