Core antigen mutations of human hepatitis B virus in hepatomas accumulate in MHC class II-restricted T cell epitopes

Seiyu Hosono, Pei Ching Tai, Wilson Wang, Mark Ambrose, Denis Guang Yu Hwang, Ta Tung Yuan, Bi Hung Peng, Czau Siung Yang, Chue Shue Lee, Chiaho Shih

Research output: Contribution to journalArticlepeer-review

71 Scopus citations


Despite the extensive molecular information on serum-derived human hepatitis B viruses (HBV), liver-derived replicative HBV genomes have remained largely uninvestigated. We have examined the sequences of the entire core antigen (nucleocapsid) of liver-derived HBVs in 15 ditferent hepatoma patients. Bona fide mutations, rather than subtype polymorphism, have been identified based on the high-frequency occurrence of structural differences from wild type at the highly evolutionarily conserved positions, instead of at the positions known to contain genetic heterogeneity among different isolates from different geographic locations. The distribution of these naturally occurring mutations of HBV core gene appears to be nonrandom and Is found predominantly within three major (I, IV, and V) and four minor domains (I, III, IV, and VII). In general, domain IV mutations correlate with domain V mutations. The replicative HBV DNAs tend to accumulate a higher number of mutated core domains than the integrated HBV DNAs. At the domain level, there is no significant difference in HBV core mutation frequencies between the liver tumors and the adjacent nontumorous livers. Strikingly, domains I, III, and V coincide with three major known T cell epitopes within the core protein in acute and chronic hepatitis B patients. Furthermore, these domains coincide with HLA class II-restricted T cell epitopes, rather than with the conventional HLA class I-restricted epitopes of cytotoxic T lymphocytes. Our results support the hypothesis that HBV core antigen variants can accomplish immunoevasion via accumulated escape mutations. In addition, they also provide a potential molecular explanation tor the maintenance of persistent infection of human hepatitis B virus In chronic carriers.

Original languageEnglish (US)
Article number71463
Pages (from-to)151-162
Number of pages12
Issue number1
StatePublished - Sep 10 1995
Externally publishedYes

ASJC Scopus subject areas

  • Virology


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