1998 Fiscal Year Final Research Report Summary
Characterization of hepatitis B virus mutant from patient with fulminant hepatitis.
| Project/Area Number |
08670630
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Gastroenterology
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| Research Institution | Tokyo Women's Medical University |
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Principal Investigator |
HASWGAWA Kiyoshi Medical Department, Tokyo Women's Medical University, 医学部, 講師 (30172886)
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| Project Period (FY) |
1996 – 1998
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| Keywords | hepatitis B virus / fulminant hepatitis / mutant / animal model |
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| Research Abstract |
We established a mouse model of hepatitis B involving liposome-mediated gene transfer, aiming to compare the antibody response to viral DNA from a patient with fulminant hepatitis with the response to wild-type viral DNA. A mixture of liposomes and full-length viral DNA was injected intrahepatically. Three days after transfection, viral transcript and antigen were detected in the liver by reverse transcription-polymerase chain reaction and immunohistochemistry. Also on day 3, hepatitis B surface antigen became detectable in the circulation. At 7 days mice of an initially nonresponding strain were reinjected, and they developed demonstrable serum antibody against viral surface antigen 5 days later. The mice transfected with the fulminant hepatitis-associated DNA produced six times the amount of antibody produced by mice transfected wild-type viral DNA. No difference was observed in amount of viral transcript or antigen in the liver or amount of in circulating hepatitis B surface antigen, suggesting that the higher antibody production in mice transfected with fulminant hepatitis-associated viral DNA resulted from increased antigenicity rather than antigen quantity. Previous DNA sequence analysis has identified mutations producing four amino acid substitutions in the envelope region compared to the wild-type virus. One or more of these amino acid changes presumably incited the hyperimmune response in mice and possibly also the patient's fulminant clinical course.
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