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

S. Hosono, P. Tai, W. Wang, M. Ambrose, D. G. Hwang, T. Yuan, Bihung Peng, C. Yang, C. Lee, C. Shih

Research output: Contribution to journalArticle

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Abstract

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)
Pages (from-to)151-162
Number of pages12
JournalVirology
Volume212
Issue number1
DOIs
StatePublished - 1995

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T-Lymphocyte Epitopes
Hepatitis B virus
Hepatocellular Carcinoma
Antigens
Mutation
Liver
Hepatitis B Core Antigens
Nucleocapsid
Geographic Locations
Genetic Heterogeneity
DNA
Chronic Hepatitis B
Cytotoxic T-Lymphocytes
Mutation Rate
Epitopes
Maintenance
Genome
Infection
Serum

ASJC Scopus subject areas

  • Virology
  • Infectious Diseases

Cite this

Hosono, S., Tai, P., Wang, W., Ambrose, M., Hwang, D. G., Yuan, T., ... Shih, C. (1995). Core antigen mutations of human hepatitis B virus in hepatomas accumulate in MHC class II-restricted T cell epitopes. Virology, 212(1), 151-162. https://doi.org/10.1006/viro.1995.1463

Core antigen mutations of human hepatitis B virus in hepatomas accumulate in MHC class II-restricted T cell epitopes. / Hosono, S.; Tai, P.; Wang, W.; Ambrose, M.; Hwang, D. G.; Yuan, T.; Peng, Bihung; Yang, C.; Lee, C.; Shih, C.

In: Virology, Vol. 212, No. 1, 1995, p. 151-162.

Research output: Contribution to journalArticle

Hosono, S, Tai, P, Wang, W, Ambrose, M, Hwang, DG, Yuan, T, Peng, B, Yang, C, Lee, C & Shih, C 1995, 'Core antigen mutations of human hepatitis B virus in hepatomas accumulate in MHC class II-restricted T cell epitopes', Virology, vol. 212, no. 1, pp. 151-162. https://doi.org/10.1006/viro.1995.1463
Hosono, S. ; Tai, P. ; Wang, W. ; Ambrose, M. ; Hwang, D. G. ; Yuan, T. ; Peng, Bihung ; Yang, C. ; Lee, C. ; Shih, C. / Core antigen mutations of human hepatitis B virus in hepatomas accumulate in MHC class II-restricted T cell epitopes. In: Virology. 1995 ; Vol. 212, No. 1. pp. 151-162.
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