Analysis of HCV quasispecies dynamic under selective pressure of combined therapy

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dc.contributorSistema FMUSP-HC: Faculdade de Medicina da Universidade de São Paulo (FMUSP) e Hospital das Clínicas da FMUSP
dc.contributor.authorJARDIM, Ana C. G.
dc.contributor.authorBITTAR, Cintia
dc.contributor.authorMATOS, Renata P. A.
dc.contributor.authorYAMASAKI, Lilian H. T.
dc.contributor.authorSILVA, Rafael A.
dc.contributor.authorPINHO, Joao R. R.
dc.contributor.authorFACHINI, Roberta M.
dc.contributor.authorCARARETO, Claudia M. A.
dc.contributor.authorCARVALHO-MELLO, Isabel M. V. G. de
dc.contributor.authorRAHAL, Paula
dc.date.accessioned2013-09-23T16:50:38Z
dc.date.available2013-09-23T16:50:38Z
dc.date.issued2013
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.
dc.description.indexMEDLINE
dc.description.sponsorshipFAPESP ""Fundacao de Amparo a Pesquisa do Estado de Sao Paulo - FAPESP"" [07/52073-0, 06/60012-9]
dc.identifier.citationBMC INFECTIOUS DISEASES, v.13, article ID 61, 16p, 2013
dc.identifier.doi10.1186/1471-2334-13-61
dc.identifier.issn1471-2334
dc.identifier.urihttps://observatorio.fm.usp.br/handle/OPI/2281
dc.language.isoeng
dc.publisherBIOMED CENTRAL LTD
dc.relation.ispartofBMC Infectious Diseases
dc.rightsopenAccess
dc.rights.holderCopyright BIOMED CENTRAL LTD
dc.subject.otherhepatitis-c virus
dc.subject.othernonstructural protein 5a
dc.subject.otherhypervariable region 1
dc.subject.otherantiviral therapy
dc.subject.otherplus ribavirin
dc.subject.otherns5a protein
dc.subject.othergenotype 1b
dc.subject.othergenetic diversity
dc.subject.othersequence-analysis
dc.subject.otherinterferon
dc.subject.wosInfectious Diseases
dc.titleAnalysis of HCV quasispecies dynamic under selective pressure of combined therapy
dc.typearticle
dc.type.categoryoriginal article
dc.type.versionpublishedVersion
dspace.entity.typePublication
hcfmusp.author.externalJARDIM, Ana C. G.:Sao Paulo State Univ, Dept Biol, Inst Biosci Language & Exact Sci, Sao Jose Do Rio Preto, SP, Brazil
hcfmusp.author.externalBITTAR, Cintia:Sao Paulo State Univ, Dept Biol, Inst Biosci Language & Exact Sci, Sao Jose Do Rio Preto, SP, Brazil
hcfmusp.author.externalMATOS, Renata P. A.:Sao Paulo State Univ, Dept Biol, Inst Biosci Language & Exact Sci, Sao Jose Do Rio Preto, SP, Brazil; Univ Fed Sao Paulo, Div Gastroenterol, Lab Appl Mol Hepatol, Hepatitis Sect, Sao Paulo, Brazil
hcfmusp.author.externalYAMASAKI, Lilian H. T.:Sao Paulo State Univ, Dept Biol, Inst Biosci Language & Exact Sci, Sao Jose Do Rio Preto, SP, Brazil
hcfmusp.author.externalFACHINI, Roberta M.:Sao Jose do Rio Preto Sch Med, Dept Hepatol, Sao Paulo, Brazil
hcfmusp.author.externalCARARETO, Claudia M. A.:Sao Paulo State Univ, Dept Biol, Inst Biosci Language & Exact Sci, Sao Jose Do Rio Preto, SP, Brazil
hcfmusp.author.externalCARVALHO-MELLO, Isabel M. V. G. de:Univ Fed Sao Paulo, Div Gastroenterol, Lab Appl Mol Hepatol, Hepatitis Sect, Sao Paulo, Brazil
hcfmusp.author.externalRAHAL, Paula:Sao Paulo State Univ, Dept Biol, Inst Biosci Language & Exact Sci, Sao Jose Do Rio Preto, SP, Brazil
hcfmusp.citation.scopus14
hcfmusp.contributor.author-fmusphcJOAO RENATO REBELLO PINHO
hcfmusp.description.articlenumber61
hcfmusp.description.volume2013
hcfmusp.origemWOS
hcfmusp.origem.pubmed23374983
hcfmusp.origem.scopus2-s2.0-84873046412
hcfmusp.origem.wosWOS:000315901300001
hcfmusp.publisher.cityLONDON
hcfmusp.publisher.countryENGLAND
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