| Project/Area Number |
16406015
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 海外学術 |
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| Research Field |
Virology
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| Research Institution | Kobe University |
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Principal Investigator |
HOTTA Hak Kobe University, Graduate School of Medicine, Professor, 大学院・医学系研究科, 教授 (40116249)
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| Co-Investigator(Kenkyū-buntansha) |
NAGANO Motoko Kobe University, Graduate School of Medicine, Assistant, 大学院・医学系研究科, 助手 (90304089)
SADA Kiyonao Kobe University, Graduate School of Medicine, Associate Professor, 大学院・医学系研究科, 助教授 (10273765)
扇本 真治 神戸大学, 大学院・医学系研究科, 助手 (80292853)
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| Project Period (FY) |
2004 – 2005
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| Project Status |
Completed (Fiscal Year 2005)
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| Budget Amount *help |
¥10,600,000 (Direct Cost: ¥10,600,000)
Fiscal Year 2005: ¥5,300,000 (Direct Cost: ¥5,300,000)
Fiscal Year 2004: ¥5,300,000 (Direct Cost: ¥5,300,000)
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| Keywords | hepatitis B virus / hepatitis C virus / sequence variation / mutant / carcinogenic risk / hepatocellular carcinoma / Indonesia / Japan / 発癌リスク / 原発性肝癌 |
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| Research Abstract |
1. Analysis of hepatitis B virus (HBV) : All of HBV isolates obtained in Surabaya, Indonesia, were classified into genotype B on the basis of partial S region sequences of the HBV genome while they were classified into genotype C on the basis of preC/C region sequences of the HBV genome. These results strongly suggest the possibility that these Indonesian HBV strains emerged through genetic recombination between genotypes B and C. There are 32 nucleotide residues (4.5% of the entire preC/C region sequence) that appear to be typical for genotype C, among which 7 residues (corresponding to 6 amino acid residues ; 2.8% of the entire preC/C peptides) are non-synonymous mutations. This recombinant type of HBV between genotypes B and C was isolated from all types of disease status, such asymptomatic carrier, chronic hepatitis, liver cirrhosis and hepatocellular carcinoma. Interestingly, HBV isolates obtained from patients with liver cirrhosis and hepatocellular carcinoma had a tendency to po
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ssess quasi-species sequences with a unique sequence at the carboxy-terminus that are rarely found in asymptomatic carriers and patients with chronic hepatitis.
2. Analysis of hepatitis C virus (HCV) : On the basis of secondary structure of the amino-terminal 120 residues of the NS3 protein, a majority of HCV isolates obtained in Surabaya, Indonesia, were classified into subgroup B1-1, which were shown to be closely associated with the occurrence of hepatocellular carcinoma in Japanese patients. Moreover, unique subgroups of HCV, which were rarely found in Japan, were frequently isolated in Indonesia. Although statistical significance was not achieved due probably to the small number of samples tested, it was interesting that HCV strains of the B1-1 subgroup prevail in Indonesia, where HCV-associated hepatocellular carcinoma is pretty common. We also observed that a considerable number of HCV isolates obtained from patients with hepatocellular carcinoma possessed four or more mutations in the interferon sensitivity-determining region (ISDR) of the NS5A protein. This result implies the possible benefit of interferon treatment for patients with HCV-associated hepatocellular carcinoma. Less
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