Analysis of Variation of Hepatitis C Viral Genome.
| Project/Area Number |
02680145
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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 |
物質生物化学
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| Research Institution | National Cancer Center |
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Principal Investigator |
KATO Nobuyuki National Cancer Center Research Institute Virology Division Research Associate, ウイルス部, 研究員 (40150883)
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| Project Period (FY) |
1990
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| Project Status |
Completed (Fiscal Year 1990)
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| Budget Amount *help |
¥1,600,000 (Direct Cost: ¥1,600,000)
Fiscal Year 1990: ¥1,600,000 (Direct Cost: ¥1,600,000)
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| Keywords | C-type hepatitis / Molecular biology / RNA virus / Virus genome / Genetic information / Nucleotide sequence / Genome structure / Structural analysis / RNAウィルス / ウィルスゲノム |
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| Research Abstract |
The genome of Japanese hepatitis C virus (HCV-J), causative agent of C-type hepatitis, has analyzed using the information of patent of Chiron Corp. containing a part of the genome structure of HCV. We have determined the nucleotide sequence of whole genomic structure of HCV-J from cDNA clones which were obtained by the amplification with RT-PCR and screening of cDNA library. HCV-J genome was 9422 nucleotides in length and had a long open reading frame of 9030 nucleotides. At the amino acid level we could find weak homology with those of the Flaviviridae, but not find any significant homology of the nucleotide sequence with other animal viruses. Therefore, we concluded that HCV-J should be classified into a new virus family distinct from the flaviviruses and pestiviruses. Comparison of HCV-J with the original isolate of HCV (HCV-US) showed 24% difference in nucleotide sequence and 15% difference in amino acid sequence and we proposed that HCV-J and HCV-US are different subtype HCV.
We ha
… More
ve also analyzed the nucleotide sequence of putative NS5 region, which encodes RNA polymerase, by RT-PCR. 19 HCV-J genomes were obtained from 16 specimens (serum of patients with hepatitis and hepatocellular carcinoma) in various areas of Japan. 14-17% of nucleotide sequence in this region was different from that of HCV-US. Furthermore, 2.5-11% of nucleotide sequence and 0-7% of amino acid sequence differed among HCV-J genomes. These results showed the heterogeneity and variation of the genomes. HCV-US types were found in Japanese hemophiliacs received imported blood products and sequence diversity (2-8% of nucleotide sequence) was found among HCV-US types. Sequence diversity of putative envelope region was also analyzed as well as RNA polymerase domain. Variation of this region was more remarkable and 12-31% of amino acid sequence differed among virus strains. Notably, we found two hypervariable regions, however, we gave to clarify the relationship between these variable regions and the mechanism of persistent infection of virus, in future. Less
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Report
(2 results)
Research Products
(20 results)
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[Publications] Kato, N., Hijikata, M., Ootsuyama, Y., Nakagawa, M., Ohkoshi, S., Sugimura, T. and Shimotohno, K.: "Molecular cloning of the human hepatitis C virus genome from Japanese patients with nonーA, nonーB hepatitis" Proc. Natl. Acad. Sci USA. 87. 9524-9528 (1990)
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[Publications] Kato, N., Hijikata, M., Ootsuyama, Y., Nakagawa, M., Ohkoshi, S. and Shimotohno, K.: "Sequence diversity of hepatitis C viral genomes" Mol. Biol. Med.7. 495-501 (1990)
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[Publications] Hijikata, M., Kato, N., Mori, S., Ootsuyama, Y., Nakagawa, M., Sugimura, T., Ohkoshi, S., Kojima, H., Meguro, T., Taki, M., Takayama, S., Yamada, K. and Shimotohno, K: "Frequent detection of hepatitis C virus US strain in Japanese Hemophiliacs" Jpn. J. Cancer Res. 81. 1195-1197 (1990)
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[Publications] Kato, N., Hijikata, M., Ootsuyama, Y., Nakagawa, M., Ohkoshi, S. and Shimotohno, K: "A structural protein encoded by the 5' region of the hepatitis C virus genome efficiently detects viral infection" Jpn. J. Cancer Res. 81. 1092-1094 (1990)
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[Publications] Hijikata, M., Kato, N., Ootsuyama, Y., Nakagawa, M., Ohkoshi, S. and Shimotohno, K: "Hypervariable regions in the putative glycoprotein of hepatitis C virus" Biochem. Biophys. Res. Commun. 175. 220-228 (1991)
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[Publications] Kato, N., Hijikata, M., Nakagawa, M., Ootsuyama, Y., Muraiso, K., Ohkoshi, S. and Shimotohno, K.: "Molecular structure of Japanese hepatitis C viral genome" FEBS Lett. 280. 325-328 (1991)
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