1991 Fiscal Year Final Research Report Summary
Clinical significance of hepatitis B inner core antigen- antibody system and pre-C mutants in chronic hepatitis B virus infection
| Project/Area Number |
01570385
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| Research Category |
Grant-in-Aid for General Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Research Field |
Gastroenterology
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| Research Institution | Yamanashi Medical College |
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Principal Investigator |
AKAHANE Yoshihiro Yamanashi Medical College, 1st Dep. of Internal Medicine, Assistant Professor, 医学部, 講師 (60092855)
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| Co-Investigator(Kenkyū-buntansha) |
MIYAZAKI Yoshiki Yamanashi Medical College, 1st Dep. of Internal Medicine, Assistant, 医学部, 助手 (80166157)
AINOTA Takao Yamanashi Medical College, 1st Dep. of Internal Medicine, Assistant, 医学部, 助手 (50167772)
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| Project Period (FY) |
1989 – 1991
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| Keywords | Hepatitis B Virus / Core Peptide / HB inner core Antigen / Pre-C region / Pre-C Mutant / Stop Codon / CAH with anti-HBe / DNA / Fulminant Hepatitis B |
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| Research Abstract |
1. The pathogenesis of HBV disease is unclear, but is believed that cytotoxic T cell might attack hepatocyte surface bearing HBc/HBe andgenicity. Recently, Machida et al reported the novel antigen sites designated as hepatitis B inner core(HBic)antigen, distinct from HBcAg or HBeAg sites.
We determined anti-HBic in sera from patients with HBV infection and detected cellular localization of HBic Ag in liver tissues. Anti-HBic was detected in sera from asymptomatic HBV carriers positive for anti-HBe. And HBic Ag was detected in hepatocytes of patients with active liver diseases by immunofluorescent technique. Patients with HBic Ag positive liver tissue did not have anti-HBic in the serum.
2. In general the presence of anti-HBe signals the remission of chronic hepatitis B. But there is a group of patients in whom hepatitis continues to progress, accompanied by high-titered DNA polymerase activity and anti-HBe in the serum. We propagated clones of HBV from the sera of patients with these disease, and showed a point mutation from guanine to adenine at nt 83 in the precore region of HBV DNA, converting codon 28 for tryptophan to a stop codon.
And we speculated that some HBV mutant with precore region defects might have higher pathogenic potential.
3. HBV clones were propagated from patients with fulminant hepatitis B. Majority of fulminant hepatitis B had a G-to-A point mutation at nt 83 in the precore region which converted codon 28 for tryptophan to a stop codon, and prohibited the synthesis and secretion of HBeAg.
By contrast, acute hepatitis B had wild type of HBV, independent of HBeAg/anti-HBe status. These data support the hypothesis that precore-defective mutant have stronger activity to induce fulminant hepatitis than wild type of HBV.
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