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Prevention and Treatment of Human Rotavirus-Induced Diarrhea in Suckling Mice

Research Project

Project/Area Number 02557024
Research Category

Grant-in-Aid for Developmental Scientific Research (B)

Allocation TypeSingle-year Grants
Research Field Virology
Research InstitutionTohoku University

Principal Investigator

EBINA Takusaburo  Tohoku University School of Medicine, Department of Bacteriology, Associate Professor, 医学部, 助教授 (60004678)

Co-Investigator(Kenkyū-buntansha) YAMAMOTO Takehiro  Taiyo Kagaku Co., Central Research Laboratories, Director, 総合研究所, 所長
Project Period (FY) 1990 – 1991
Project Status Completed (Fiscal Year 1991)
Budget Amount *help
¥5,900,000 (Direct Cost: ¥5,900,000)
Fiscal Year 1991: ¥2,200,000 (Direct Cost: ¥2,200,000)
Fiscal Year 1990: ¥3,700,000 (Direct Cost: ¥3,700,000)
KeywordsRotavirus / Infantile diarrhea / Passive immunity / Antiviral agents / Colostrum / Protease inhibitor / Biological response modifier / Suckling mice / オボシスタチン / BALB / cマウス / E-64 / 卵黄免疫グロブリン / 担子菌製剤 / c マウス
Research Abstract

Orai inoculation of human rotavirus MO strain (serotype 3) into 5 day old BALB/c mice caused gastroenteritis characterized by diarrhea. Using this small animal model, passive protection of suckling mice against human rotavirus infection was achieved with the use of immunoglobulin (IgY) from the yolks of eggs of rotavirus-immunized hens. When IgY against a rotavirus strain homotypic to the challenge virus (MO strain) was administered in the mice, complete protection against rotavirus infection was achieved. On the other hand, with oral administration of IgY against a heterotypic strain (serotype 1, Wa strain), a lower protective effect was nevertheless obtained.
After immunizing 8-month pregnant Holstein cows with human rotavirus MO strain, cow colostrum containing neutraliozing antibody to 4 different serotypes of human rotavirus, designated as Rota colostrum, was obtained. Rota colostrum completely protected the rotavirus infection, but purified IgG or IgA obtained from Rota colostrum … More was unable to protect the rotavirus infection. After randomly grouping 20 infants from a baby care center, 10 infants received 20 ml of Rota colostrum per day for 2 weeks and 10 control infants did not. Rotavirus associated diarrhea developed in 7 out of the 10 infants in the control group. None of the 3 infants in the Rota colostrum every day recipient group showed such symptoms and one out of 3 infants in the every other day recipient group developed rotavirus induced diarrhea. All 4 infants who received Rota colostrum after appearing symptoms developed diarrhea.
The different four strains of human rotavirus (Wa, KUN, MO and ST3) were inactivated in vitro by treatment with PSK, a protein-bound plysaccharide preparation, in a dose-dependent manner. Oral administration of 2.5 mg of PSK caused a therapeutic effect on experimentally MO-infected suckling mice. The antiviral effect of PSK was indicated by the reduction of the duration of diarrhea.
The infectivity of human rotavirus was enhanced by treatment of protease in vitro. A cysteine protease inhibitor, E-64-c, was given orally at 12 hrs and 24 hrs after MO infection. Oral administration of 0.3 mg of E-64-c prevented the diarrhea at 17.5% on day 2 and 10% on day 3. Oral administration of 0.15 mg of cysteine protease inhibitor, ovocystatin, completely prevented the diarrhea on day 2. Serine protease inhibitor, aprotinin (0.15 mg x 2), also prevented the diarrhea on day 2 at 14.3%. These protease inhibitors were nontoxic in vitro and to suckling mice. Less

Report

(3 results)
  • 1991 Annual Research Report   Final Research Report Summary
  • 1990 Annual Research Report
  • Research Products

    (14 results)

All Other

All Publications (14 results)

  • [Publications] Takusaburo EBINA: "Passive Immunizations of suckling Mice and Infants with Bovine Colostrum Containing Antibodies to Human Rotavirus" Journal of Medical virology. (1992)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1991 Final Research Report Summary
  • [Publications] Takusaburo EBINA: "Protease Inhibitors Prevent the Development of Human Rotavirus-Induced Diarrhea is Suckling Mice" Microbiology and Immunology. 35. 583-588 (1991)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1991 Final Research Report Summary
  • [Publications] Takusaburo EBINA: "Gastroenteritis in Suckling Mice Caused by Human Rotavirus Can be prevented with Egg Yolk Immunoglobulin(IgY)and Treated with a Protein-Bound polysaccharide Preparation(PSK)" Microbiolgy and Immunology. 34. 317-629 (1990)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1991 Final Research Report Summary
  • [Publications] 海老名 卓三郎: "乳幼児下痢症ーロタウイルス下痢症の予防と治療を中心に" Journal of Antibacterial and Antifungal Agents. 19. 349-358 (1991)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1991 Final Research Report Summary
  • [Publications] 海老名 卓三郎: "ロタウイルス免疫牛初乳並びに卵黄IgYによる下痢症の予防" Japanese Journal of Dairy and Food Science. 40. 324-331 (1991)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1991 Final Research Report Summary
  • [Publications] 海老名 卓三郎: "抗ウイルス剤の新しい標的ー可溶性ウイルス受容体とプロテア-ゼ阻害剤ー" 医学のあゆみ. 153. 624 (1990)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1991 Final Research Report Summary
  • [Publications] Takusaburo EBINA et al.: "Passive Immunizations of Suckling mice and Infants with Bovine Colostrum Containing Antibodies to Human Rotavirus" Journal of Medical Virology. (1992)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1991 Final Research Report Summary
  • [Publications] Takusaburo EBINA et al.: "Protease Inhibitors Prevent the Development of Human Rotavirus-Induced Diarrhea in Suckling Mice" Microbiology and Immunology. 35. 583-588 (1991)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1991 Final Research Report Summary
  • [Publications] Takusaburo EBINA et al.: "Gastroenteritis in Suckling Mice Caused Human Rotavirus Can Be Prevented with Egg Yolk Immunoglobulin (IgY) and Treated with a Protein-Bound Polysaccharide Preparation (PSK)" Microbiology and Immunology. 34. 617-629 (1991)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1991 Final Research Report Summary
  • [Publications] Takusaburo EBINA: "Protease Inhibitors Prevent the Development of Human Rotavirus-Induced Diarrhea in Suckling Mice" Microbiology and Immunology. 35. 583-588 (1991)

    • Related Report
      1991 Annual Research Report
  • [Publications] Takusaburo EBINA: "Passive Immunizations of Suckling Mice and Infants with Bovine Colostrum Containing Antibodies to Human Rotavirus" Journal of Medical Virology.

    • Related Report
      1991 Annual Research Report
  • [Publications] 海老名 卓三郎: "乳幼児下痢症ーロタウイルス下痢症の予防と治療を中心に" 防菌防黴雑誌. 19. 349-358 (1991)

    • Related Report
      1991 Annual Research Report
  • [Publications] 海老名 卓三郎: "ロタウイルス免疫牛初乳並びに卵黄IgYによる下痢症の予防" Japanese Journal of Dairy and food Science. 40. 323-331 (1991)

    • Related Report
      1991 Annual Research Report
  • [Publications] Takusaburo EBINA: "Gastroenteritis in Suckling Mice Caused by Human Rotavirus Can be Prevented with Egg Yolk Immunoglobulin (IgY) and Treated with a Proteinーbound Polysaccharide Preparation (PSK)" Microbiology and Immunology. 34. 617-629 (1990)

    • Related Report
      1990 Annual Research Report

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Published: 1990-04-01   Modified: 2016-04-21  

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