2.50
Hdl Handle:
http://hdl.handle.net/10033/71213
Title:
Evolution of hepatitis C virus hypervariable region 1 in immunocompetent children born to HCV-infected mothers.
Authors:
Gismondi, M I; Becker, P D; Díaz Carrasco, J M; Guzmán, C A; Campos, R H; Preciado, M V
Abstract:
Hepatitis C virus (HCV) hypervariable region 1 (HVR1) is the most variable region of the viral genome and its heterogeneity reflects the virus-host interplay during chronicity. Paediatric HCV-infected patients develop liver disease with typical clinical features. Here, the evolution of HVR1 and its adjacent regions were ascertained in plasma samples of two HCV-positive children during a 5-year follow-up period. We report an almost complete conservation of the HVR1 amino acid sequence over time, with underlying nucleotide variability both within and outside HVR1, suggesting some kind of constraint on virus evolution, particularly within HVR1. Although overall d(N)/d(S) rates [rates of nonsynonymous nucleotide substitutions per nonsynonymous site (d(N)) and synonymous nucleotide substitutions per synonymous site (d(S))] were <1 in both patients, a high resolution analysis of selection pressures exerted at the codon level revealed few sites subject to selection and an absolute predominance of invariable positions within HVR1. The HVR1 amino acid sequences showed the antigenic properties expected for this region. Taken together, these data suggest peculiar evolutionary dynamics in our patients, which could be attributed to a mechanism of nucleotide invariability along with purifying selection operating on the HVR1. The lack of HVR1 variability may reflect the adaptation of the virus to a particular environment within each patient or a phenomenon of immune tolerance generated in these immunocompetent patients earlier in life.
Affiliation:
Laboratorio de Biología Molecular, División Patología, Hospital de Niños Ricardo Gutiérrez, Buenos Aires, Argentina.
Citation:
Evolution of hepatitis C virus hypervariable region 1 in immunocompetent children born to HCV-infected mothers. 2009, 16 (5):332-9 J. Viral Hepat.
Journal:
Journal of viral hepatitis
Issue Date:
May-2009
URI:
http://hdl.handle.net/10033/71213
DOI:
10.1111/j.1365-2893.2009.01071.x
PubMed ID:
19228286
Type:
Article
Language:
en
ISSN:
1365-2893
Appears in Collections:
publications of the research group vaccinology and applied microbiology (VAC)

Full metadata record

DC FieldValue Language
dc.contributor.authorGismondi, M I-
dc.contributor.authorBecker, P D-
dc.contributor.authorDíaz Carrasco, J M-
dc.contributor.authorGuzmán, C A-
dc.contributor.authorCampos, R H-
dc.contributor.authorPreciado, M V-
dc.date.accessioned2009-06-23T08:07:33Z-
dc.date.available2009-06-23T08:07:33Z-
dc.date.issued2009-05-
dc.identifier.citationEvolution of hepatitis C virus hypervariable region 1 in immunocompetent children born to HCV-infected mothers. 2009, 16 (5):332-9 J. Viral Hepat.en
dc.identifier.issn1365-2893-
dc.identifier.pmid19228286-
dc.identifier.doi10.1111/j.1365-2893.2009.01071.x-
dc.identifier.urihttp://hdl.handle.net/10033/71213-
dc.description.abstractHepatitis C virus (HCV) hypervariable region 1 (HVR1) is the most variable region of the viral genome and its heterogeneity reflects the virus-host interplay during chronicity. Paediatric HCV-infected patients develop liver disease with typical clinical features. Here, the evolution of HVR1 and its adjacent regions were ascertained in plasma samples of two HCV-positive children during a 5-year follow-up period. We report an almost complete conservation of the HVR1 amino acid sequence over time, with underlying nucleotide variability both within and outside HVR1, suggesting some kind of constraint on virus evolution, particularly within HVR1. Although overall d(N)/d(S) rates [rates of nonsynonymous nucleotide substitutions per nonsynonymous site (d(N)) and synonymous nucleotide substitutions per synonymous site (d(S))] were <1 in both patients, a high resolution analysis of selection pressures exerted at the codon level revealed few sites subject to selection and an absolute predominance of invariable positions within HVR1. The HVR1 amino acid sequences showed the antigenic properties expected for this region. Taken together, these data suggest peculiar evolutionary dynamics in our patients, which could be attributed to a mechanism of nucleotide invariability along with purifying selection operating on the HVR1. The lack of HVR1 variability may reflect the adaptation of the virus to a particular environment within each patient or a phenomenon of immune tolerance generated in these immunocompetent patients earlier in life.en
dc.language.isoenen
dc.subject.meshAmino Acid Sequenceen
dc.subject.meshChild, Preschoolen
dc.subject.meshConserved Sequenceen
dc.subject.meshEvolution, Molecularen
dc.subject.meshFollow-Up Studiesen
dc.subject.meshHepacivirusen
dc.subject.meshHepatitis C, Chronicen
dc.subject.meshHumansen
dc.subject.meshMolecular Sequence Dataen
dc.subject.meshMutation, Missenseen
dc.subject.meshPlasmaen
dc.subject.meshPoint Mutationen
dc.subject.meshSelection (Genetics)en
dc.subject.meshSequence Analysis, DNAen
dc.titleEvolution of hepatitis C virus hypervariable region 1 in immunocompetent children born to HCV-infected mothers.en
dc.typeArticleen
dc.contributor.departmentLaboratorio de Biología Molecular, División Patología, Hospital de Niños Ricardo Gutiérrez, Buenos Aires, Argentina.en
dc.identifier.journalJournal of viral hepatitisen

Related articles on PubMed

This item is licensed under a Creative Commons License
Creative Commons
All Items in HZI are protected by copyright, with all rights reserved, unless otherwise indicated.