title: Hepatitis B virus core protein mutations are concentrated in B cell epitopes in progressive disease and in T helper cell epitopes during clinical remission.
abstract: The distribution and temporal and clinical features of amino acid substitutions of the core protein of hepatitis B (HB) virus were analyzed, using at least 2 sequential samples from 27 patients. Six patients seroconverted from HBe antigen (HBeAg)-positive to anti-HBe-positive (3 went into remission), and 21 were continuously anti-HBe positive with progressive hepatitis. Precore mutations, which terminate HBeAg translation, all appeared by the second sample. Most core mutations occurred between the first and second samples; significantly fewer occurred after the second. In seroconverters who went into remission, mutations occurred in the T helper epitope from aa 50 to 69 (P = .00045); for anti-HBe-positive patients with ongoing disease, mutations occurred in B cell epitopes (P = .0007 for aa 74-83). An ineffective anti-HBc B cell response accounts for ongoing disease and selection of mutations after seroconversion. In those who remit, mutations in the major T helper epitope allow immune escape, thus minimizing immune-mediated hepatitis.
authors.affiliation: Institute of Virology, University of Glasgow, United Kingdom.
authors.forename: W F
authors.initials: WF
authors.lastname: Carman
authors.forename: W
authors.initials: W
authors.lastname: Boner
authors.forename: G
authors.initials: G
authors.lastname: Fattovich
authors.forename: K
authors.initials: K
authors.lastname: Colman
authors.forename: E S
authors.initials: ES
authors.lastname: Dornan
authors.forename: M
authors.initials: M
authors.lastname: Thursz
authors.forename: S
authors.initials: S
authors.lastname: Hadziyannis
mesh_terms: D000328:Adult; D000368:Aged; D000595:Amino Acid Sequence; D004279:DNA, Viral / Q000097:blood; D000939:Epitopes / Q000032:analysis; D005260:Female; D006115:Greece; D006509:Hepatitis B / Q000097:blood / Q000276:immunology*; D006512:Hepatitis B Core Antigens / Q000235:genetics* / Q000276:immunology; D006513:Hepatitis B e Antigens / Q000235:genetics* / Q000276:immunology; D006515:Hepatitis B virus / Q000235:genetics*; D006801:Humans; D008297:Male; D008875:Middle Aged; D017354:Point Mutation; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology*
chemical_list: D004279:DNA, Viral; D000939:Epitopes; D006512:Hepatitis B Core Antigens; D006513:Hepatitis B e Antigens