HBV Core Region Variability: Effect of Antiviral Treatments on Main Epitopic Regions

Maria Homs; Rosendo Jardi; Maria Buti; Melanie Schaper; David Tabernero; Pilar Fernandez-Fernandez; Josep Quer; Rafael Esteban; Francisco Rodriguez-Frias

doi:10.3851/imp1701

journal article Jan 01, 2011

HBV Core Region Variability: Effect of Antiviral Treatments on Main Epitopic Regions

Maria Homs Rosendo Jardi Maria Buti

Melanie Schaper David Tabernero

Pilar Fernandez-Fernandez Josep Quer

Rafael Esteban Francisco Rodriguez-Frias

Antiviral Therapy Vol. 16 No. 1 pp. 37-49 · SAGE Publications

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Abstract

Background Amino acid (AA) changes in specific hepatitis B core antigen (HBcAg) regions were assessed in patients infected with chronic hepatitis B (CHB) after a 12-month untreated period and after receiving antiviral therapy (interferon, lamivudine or adefovir dipivoxil), and in inactive hepatitis B surface antigen-positive carriers. Methods Samples corresponding to different time points in 76 CHB cases (64 on-treatment) and 4 inactive carriers were included. The main precore mutation, T-helper immunodominant epitope at AA 50–69 (Th50–69), minor T-helper epitope (Th28–47), B-cell immunodominant epitope (B74–84) and a conserved region of HBcAg at AA 1–11 (AA1–11) were directly sequenced. For comparisons, the average number of AA changes in each region was standardized to 12 months (Av12). Results AA changes clustered mainly in immunodominant regions (69%). The highest percentage of cases (% n) with changes and highest Av12 changes were detected after interferon treatment (% n=73%, Av12=3.1 in Th50–69 and % n=86%, Av12=2.7 in B74–84). At baseline, immunodominant regions had higher Av12 changes in hepatitis B e antigen-negative patients and those with main precore mutations. Changes in the Th28–47 region were more frequent after nucleoside/nucleotide analogue treatment (40%) than before treatment (9%). Codons 74 and 77 were the most polymorphic, and the double change E64D-N67T was significantly observed. Codon 84 substitutions were mainly associated with interferon treatment ( P=0.05). Conclusions Natural and treatment-induced substitutions in HBV core protein, occurring especially with interferon treatment, were characterized. Some immune-stimulating activity related to the minor Th28–47 epitope might be associated with nucleoside/nucleotide analogues; this activity was also seen in inactive carriers.

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Details

Published: Jan 01, 2011
Vol/Issue: 16(1)
Pages: 37-49
License: View

Authors

M

Maria Homs

Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Instituto Carlos III, Madrid, Spain; Department of Biochemistry, Hospital Universitari Vall d'Hebron, Universitat Autonòma de Barcelona, Barcelona, Spain

R

Rosendo Jardi

Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Instituto Carlos III, Madrid, Spain; Department of Biochemistry, Hospital Universitari Vall d'Hebron, Universitat Autonòma de Barcelona, Barcelona, Spain

M

Maria Buti

Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Instituto Carlos III, Madrid, Spain; Department of Hepatology, Hospital Universitari Vall d'Hebron, Universitat Autonòma de Barcelona, Barcelona, Spain

M

Melanie Schaper

Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Instituto Carlos III, Madrid, Spain; Department of Biochemistry, Hospital Universitari Vall d'Hebron, Universitat Autonòma de Barcelona, Barcelona, Spain

D

David Tabernero

Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Instituto Carlos III, Madrid, Spain; Department of Biochemistry, Hospital Universitari Vall d'Hebron, Universitat Autonòma de Barcelona, Barcelona, Spain

P

Pilar Fernandez-Fernandez

Department of Biochemistry, Hospital Universitari Vall d'Hebron, Universitat Autonòma de Barcelona, Barcelona, Spain

J

Josep Quer

Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Instituto Carlos III, Madrid, Spain; Department of Hepatology, Hospital Universitari Vall d'Hebron, Universitat Autonòma de Barcelona, Barcelona, Spain

R

Rafael Esteban

Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Instituto Carlos III, Madrid, Spain; Department of Hepatology, Hospital Universitari Vall d'Hebron, Universitat Autonòma de Barcelona, Barcelona, Spain

F

Francisco Rodriguez-Frias

Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Instituto Carlos III, Madrid, Spain; Department of Biochemistry, Hospital Universitari Vall d'Hebron, Universitat Autonòma de Barcelona, Barcelona, Spain

Cite This Article

Maria Homs, Rosendo Jardi, Maria Buti, et al. (2011). HBV Core Region Variability: Effect of Antiviral Treatments on Main Epitopic Regions. Antiviral Therapy, 16(1), 37-49. https://doi.org/10.3851/imp1701

HBV Core Region Variability: Effect of Antiviral Treatments on Main Epitopic Regions

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