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Establishment of animal model of hepatitis C virus infection and examination of vaccine effects.

Research Project

Project/Area Number13670295
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Virology
Research InstitutionMie University

Principal Investigator

YASUTOMI Yasuhiro  Mie University, Faculty of Medicine, Associate Professor, 医学部, 助教授 (90281724)

Project Period (FY) 2001 – 2002
Project Status Completed(Fiscal Year 2002)
Budget Amount *help
¥3,400,000 (Direct Cost : ¥3,400,000)
Fiscal Year 2002 : ¥1,600,000 (Direct Cost : ¥1,600,000)
Fiscal Year 2001 : ¥1,800,000 (Direct Cost : ¥1,800,000)
Keywordsvaccine / immunology / HCV / Adenovirus vector / hepatitis / アデノウィルスベクター / CTL / 感染モデル
Research Abstract

Hepatitis C virus (HCV) is one of the major agents of chronic hepatitis and liver disease worldwide. An animal model for HCV infection is required for both vaccine development and for understanding the pathogenesis of HCV infection. Although the chimpanzee is the only known animal model of HCV infection, chimpanzees are difficult to acquire for laboratory animals. In the present study, we assessed the possibility of infection with recombinant adenovirus (rADV-HCV), which is preferential infection to hepatocytes, having cDNA of HCV structural proteins in mice as a novel animal model. Mice were intravascularly inoculated with rADV-HCV. After rADV-HCV inoculation, concentrations of GPT in sera were increased and much higher than control rADV having cDNA of lacZ. These mice inoculated with rADV-HCV showed acute hepatitis in histopathological examination but not control rADV. These high concentrations of GPT in sera were observed for 2 weeks after infection. The HCV-specific CD8+ cytotoxic T lymphocytes (CTLs) were observed after infection with rADV-HCV. The concentrations of GPT in sera were not increased after infection with rADV-HCV, when FK506 or anti-CD8 monoclonal antibody was administered with mice to eliminate these HCV specific CTLs. These studies demonstrated the capacity of murine model induced by inoculation with rADV-HCV to elicit HCV-specific CTL in association with pathogenesis of HCV infection.

Report

(3results)
  • 2002 Annual Research Report   Final Research Report Summary
  • 2001 Annual Research Report

Research Products

(22results)

All Other

All Publications

  • [Publications] Uno-Furuta, S., Tamaki, S., Takebe, Y., Takamura, S., Kamei, A., Kim, G., Kuromatsu, I., Kaito, M., Adachi, Y., Yasutomi, Y.: "Induction of virus-specific cytotoxic T lymphocytes by in vivo electric administration of peptides"Vaccine. 19. 2190-2196 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Mori, K., Yasutomi, Y., Ohgimoto, S., Nakasone, T., Takamura, S., Shioda, T., Nagai, Y.: "Quintuple Deglycosylation Mutant of Simian Immunodeficiency Virus SIVmac239 in Rhesus Macaques : Robust Primary Replication, Tightly Contained Chronic Infection, and Elicitation of Potent Immunity against the Parental Wild-Type Strain"J. Virol. 75. 4023-4028 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Niikura, M., Takamura, S., Kim, G., Kawai, S., Saijo, M., Morikawa, S., Kurane, I., Tian-Cheng Li, Takeda, N., Yasutomi, Y.: "Chimeric recombinant hepatitis E virus -like particles as an oral vaccine vehicle presenting foreign epitopes"Virology. 273-280 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Imanaka-Yoshida, K., Hiroe, M., Yasutomi, Y., Maki, S., Tsuchiya, T., Noda, N., Toyozaki, T., Nishikawa, T., Ishiyama, S., Sakakura, T., Yoshida, T.: "Tenascin-C is a Useful Marker for Disease Activity in Myocarditis"Journal of Pathology. 197. 388-394 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Mukai, K., Yasutomi, Y., Watanabe, M., Kenjo, A., Aota, T., Wang, L., Nishikawa, H., Fujita, T., Kuribayashi, K., Suzuki, H.: "HER2 peptide-specific CD8+T cells are proportionally detectable long after multiple DNA vaccinations"Gene Therapy. 9. 879-888 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Uno-Furuta, S., Matsuo, K., Tamaki, S., Takamura, S., Kamei, A., Kuromatsu, I., Kaito, M., Matsuura Y., Miyamura, T., Adachi, Y., Yasutomi, Y.: "Immunization with recombinant bacillus Calmette-Guerin (BCG)-hepatitis C virus (HCV) elicits HCV-specific cytotoxic T lymphocytes in mice"Vaccine. (印刷中). (2003)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Uno-Furuta,S., Tamaki,S., Takebe,Y., Takamura,S., Kamei,A., Kim,G., Kuromatsu,I., Kaito,M., Adachi,Y.and Yasutomi,Y.: "Induction of virus-specific cytotoxic T lymphocytes by in vivo electric administration of peptides"Vaccine. 19. 2190-2196 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Mori,K., Yasutomi,Y., Ohgimoto,S., Nakasone,T., Takamura,S., Shioda,T.and Nagai,Y.: "Quintiple deglycosylated mutant of simian immunodeficiency virus SIV mac239 in rhesus macaques : Robust primary replication, tightly contained hronic infection and elicitation of potent immunity against the parental wild-type strain"J.Virol.. 75. 4023-4028 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Niikura,M., Takamura,S., Kim,G., Kawai,S., Saijo,M., Morikawa,S., Kurane,I., Tian-Cheng Li, Takeda,N.and Yasutomi,Y.: "Chimeric recombinant hepatitis E virus-like particles as an oral vaccine vehicle presenting foreign epitopes"Virology. 293. 273-280 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Imanaka-Yoshida,K., Hiroe,M., Yasutomi,Y., Maki,S., Tsuchiya,T., Noda,N., Toyozaki,T., Noshikawa,T., Ishiyama,S., Sakakura,T.and Yoshida,T.: "Tenascin-C is a Useful Marker for Disease Activity in Myocarditis"J.Pathol.. 197. 388-394 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Mukai,K., Yasutomi,Y., Watanabe,M., Kenjo,A., Aota,T., Wang,L., Noshikawa,H., Fujita,T., Kuribayashi,K.and Shiku,H.: "HER2 peptide-specific CD8+ T cells are proportionally detectable long after multiple DNA vaccinations"Gene Ther.. 9. 879-888 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Uno-Furuta,S., Matsuo,K., Tamaki,S., Takamura,S., Kamei,A., Kuromatsu,I., Kaito,M., Matsuura,Y., Miyamura,T., Adachi,Y., and Yasutomi,Y.: "Immunization with recombinant bacillus Calmette-Guerin (BCG)-hepatitis C virus (HCV) elicitis HCV-specific cytotoxic T lymphocytes in mice"Vaccine. in press.

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Niikura, M., Takamura, S., Kim, G., Kawai, S., Saijo, M., Morikawa, S., Kurane, I., Tian-Cheng Li, Takeda, N., Yasutomi, Y.: "Chimeric recombinant hepatitis hepatitis E virus-like particles as an oral vaccine vehicle presenting foreign epitopes"Virology. 293. 273-280 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Imanaka-Yoshida, K., Hiroe, M., Yasutomi, Y., Maki, S., Tsuchiya, T., Noda, N., Toyozaki, T., Nishikawa, T., Ishiyama, S., Sakakura, T., Yoshida, T.: "Tenascin-C is a Useful Marker for Disease Activity in Myocarditis"Journal of Pathology. 197. 388-394 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Mukai, K., Yasutomi, Y., Watanabe, M., Kenjo, A., Aota, T., Wang, L., Nishikawa, H., Fujita, T., Kuribayashi, K., Shiku, H.: "HER2 peptide-specific CD8^+ T cells are proportionally detectable long after multiple DNA vaccinations"Gene Therapy. 9. 879-888 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Uno-furuta, S., Matsuo, K., Tamaki, S., Takamura, S., Kamei, A., Kuromatsu, I., Kaito, M., Matsuura, Y., Miyamura, T., Adachi, Y., Yasutomi, Y.: "Immunization with recombinant bacillus Calmette-Guerin(BCG)-hepatitis C virus(HCV) elicits HCV-specific cytotoxic T lymphocytes in mice"Vaccine. (印刷中). (2003)

    • Related Report
      2002 Annual Research Report
  • [Publications] Uno-Furuta, S., et.al.: "Induction of virus-specific cytotoxic T lymphocytes by in vivo electric administration of peptides"Vaccine. 19. 2190-2196 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Iwanami, N., et.al.: "Role of natural killer cells in resistance against Friend retrovirus-induced leikemia"J.Virol.. 75. 3152-3163 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Mori, K., et.al.: "Quintiple deglycosylated mutant of simian immunodeficiency virus SIVmac239 in rhesus macaques:Robust primary replication,tightly contained…"J.Virol.. 75. 4023-4028 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Kuromatsu, I., et.al.: "Induction of effective antitumor immune responses by using DNA of an α Ag from mycobacteria"Cancer Gene Ther.. 8. 483-490 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Niikura, M., et.al.: "Chimeric recombinant hepatitis E virus-like particles as an oral vaccine vehicle presenting foreign epitopes"Virology. (印刷中).

    • Related Report
      2001 Annual Research Report
  • [Publications] Imanaka-Yoshida, K., et.al.: "Tenascin-C is a Useful Marker for Disease Activity in Myocarditis"J.Pathol.. (印刷中).

    • Related Report
      2001 Annual Research Report

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Published : 2001-04-01   Modified : 2016-04-21  

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