title: HBV core region variability: effect of antiviral treatments on main epitopic regions.
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.
authors.affiliation: Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Instituto Carlos III, Madrid, Spain.
authors.forename: Maria
authors.initials: M
authors.lastname: Homs
authors.forename: Rosendo
authors.initials: R
authors.lastname: Jardi
authors.forename: Maria
authors.initials: M
authors.lastname: Buti
authors.forename: Melanie
authors.initials: M
authors.lastname: Schaper
authors.forename: David
authors.initials: D
authors.lastname: Tabernero
authors.forename: Pilar
authors.initials: P
authors.lastname: Fernandez-Fernandez
authors.forename: Josep
authors.initials: J
authors.lastname: Quer
authors.forename: Rafael
authors.initials: R
authors.lastname: Esteban
authors.forename: Francisco
authors.initials: F
authors.lastname: Rodriguez-Frias
mesh_terms: D000225:Adenine / Q000008:administration & dosage / Q000031:analogs & derivatives / Q000276:immunology / Q000627:therapeutic use; D000328:Adult; D000595:Amino Acid Sequence; D000940:Antigenic Variation / Q000187:drug effects; D000998:Antiviral Agents / Q000008:administration & dosage / Q000276:immunology / Q000627:therapeutic use; D001402:B-Lymphocytes / Q000276:immunology / Q000821:virology; D004279:DNA, Viral / Q000737:chemistry*; D024882:Drug Resistance, Viral / Q000187:drug effects; D005260:Female; D006512:Hepatitis B Core Antigens / Q000235:genetics* / Q000276:immunology; D006515:Hepatitis B virus / Q000187:drug effects / Q000235:genetics* / Q000276:immunology; D019694:Hepatitis B, Chronic / Q000188:drug therapy / Q000235:genetics* / Q000276:immunology / Q000821:virology; D006801:Humans; D016056:Immunodominant Epitopes / Q000737:chemistry*; D007372:Interferons / Q000008:administration & dosage / Q000276:immunology / Q000627:therapeutic use; D019259:Lamivudine / Q000008:administration & dosage / Q000276:immunology / Q000627:therapeutic use; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D009154:Mutation; D063065:Organophosphonates / Q000008:administration & dosage / Q000276:immunology / Q000627:therapeutic use; D011110:Polymorphism, Genetic; D013601:T-Lymphocytes / Q000276:immunology / Q000821:virology
chemical_list: D000998:Antiviral Agents; D004279:DNA, Viral; D006512:Hepatitis B Core Antigens; D016056:Immunodominant Epitopes; D063065:Organophosphonates; D019259:Lamivudine; D007372:Interferons; D000225:Adenine; C106812:adefovir dipivoxil