Sequence variation of hepatitis B virus precore-core open reading frame isolated from serum and liver of children with chronic hepatitis B before and after interferon treatment.
DNA and amino acid sequences of the hepatitis B virus (HBV) genome were studied in serum and liver samples taken from 12 children with chronic hepatitis B before and after interferon (IFN) therapy. The purpose was to discover whether the persistence of low levels of viral replication with normal alanine aminotransferases after the response to IFN treatment is due to the appearance of mutations in the sequence of HB core antigen T and B cell epitopes. The existence of mutants was studied by amplification of precore-core region of the HBV genome by polymerase chain reaction (PCR) and direct sequencing of the PCR products. In addition to the wild type sequence, mutation 1896 in the precore region was detected in the baseline serum and liver samples of five children. No changes in the distribution were found in the final samples, except one case. In the core region, both the wild type sequence and amino acid substitutions were observed in the basal serum and/or liver samples of six patients and most of these remained detectable in the samples after treatment. Sixteen (67%) of 24 changes in the core amino acid sequences were found in the T- or B-cell epitopes. The results suggest that viral persistence after response to IFN therapy in children is not due to the appearance of mutants in the HBV core T- and B-cell epitopes and that the host immune response can control the viral replication.
Cabrerizo
M
M
Department of Hepatology, Fundación Jiménez Díaz, Madrid, Spain.
Bartolomé
J
J
Otero
M
M
Ruiz-Moreno
M
M
Carreño
V
V
D000410:Alanine Transaminase / Q000097:blood / Q000187:drug effects; D019943:Amino Acid Substitution; D000998:Antiviral Agents / Q000627:therapeutic use*; D002648:Child; D004252:DNA Mutational Analysis; D004279:DNA, Viral / Q000097:blood / Q000737:chemistry / Q000187:drug effects; D014644:Genetic Variation; D006512:Hepatitis B Core Antigens / Q000097:blood / Q000187:drug effects* / Q000235:genetics; D006513:Hepatitis B e Antigens / Q000097:blood / Q000187:drug effects; D006515:Hepatitis B virus / Q000187:drug effects* / Q000235:genetics; D019694:Hepatitis B, Chronic / Q000188:drug therapy* / Q000235:genetics; D006801:Humans; D007372:Interferons / Q000627:therapeutic use*; D008099:Liver / Q000187:drug effects* / Q000378:metabolism / Q000821:virology; D016366:Open Reading Frames; D017354:Point Mutation; D016133:Polymerase Chain Reaction
D000998:Antiviral Agents; D004279:DNA, Viral; D006512:Hepatitis B Core Antigens; D006513:Hepatitis B e Antigens; D007372:Interferons; D000410:Alanine Transaminase