1991 Fiscal Year Final Research Report Summary
Prevention and Treatment of Human Rotavirus-Induced Diarrhea in Suckling Mice
| Project/Area Number |
02557024
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| Research Category |
Grant-in-Aid for Developmental Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Research Field |
Virology
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| Research Institution | Tohoku University |
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Principal Investigator |
EBINA Takusaburo Tohoku University School of Medicine, Department of Bacteriology, Associate Professor, 医学部, 助教授 (60004678)
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| Co-Investigator(Kenkyū-buntansha) |
YAMAMOTO Takehiro Taiyo Kagaku Co., Central Research Laboratories, Director, 総合研究所, 所長
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| Project Period (FY) |
1990 – 1991
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| Keywords | Rotavirus / Infantile diarrhea / Passive immunity / Antiviral agents / Colostrum / Protease inhibitor / Biological response modifier / Suckling mice |
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| 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
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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
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