| Project/Area Number |
11470058
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Experimental pathology
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| Research Institution | OKAYAMA UNIVERSITY |
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Principal Investigator |
HAYASHI Kazuhiko OKAYAMA UNIVERSITY, GRADUATE SCHOOL OF MEDICINE AND DENTISTRY, ASSOCIATE PROFESSOR, 大学院・医歯学総合研究科, 助教授 (30180962)
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| Co-Investigator(Kenkyū-buntansha) |
OHARA Nobuya OKAYAMA UNIVERSITY, HOSPITAL, ASSISTANT, 医学部・附属病院, 助手 (90325100)
OKA Takashi OKAYAMA UNIVERSITY, GRADUATE SCHOOL OF MEDICINE AND DENTISTRY, ASSISTANT, 大学院・医歯学総合研究科, 助手 (50160651)
KONDO Eisaku OKAYAMA UNIVERSITY, GRADUATE SCHOOL OF MEDICINE AND DENTISTRY, ASSISTANT, 大学院・医歯学総合研究科, 助手 (30252951)
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| Project Period (FY) |
1999 – 2001
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| Project Status |
Completed (Fiscal Year 2001)
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| Budget Amount *help |
¥9,400,000 (Direct Cost: ¥9,400,000)
Fiscal Year 2001: ¥1,800,000 (Direct Cost: ¥1,800,000)
Fiscal Year 2000: ¥2,000,000 (Direct Cost: ¥2,000,000)
Fiscal Year 1999: ¥5,600,000 (Direct Cost: ¥5,600,000)
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| Keywords | EBV / MALIGNANT LYMPHOMA / RABBIT / HEMOPHAGOCYTIC SYNDROME / MONKEY / HVP / ANIMAL MODEL / LYMPHOCRYPTOVIRUS / 血球貧食症候群 / EVウイルス / 悪性リンパ腫 / ヘルペスウイルス / EBウイルス |
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| Research Abstract |
Animal models of human EBV-associated diseases are essential to elucidate the pathogenesis of EBV-infection and EBV-associated diseases. Here we reported our two newly developed rabbit models of lymphoproliferative diseases (LPD) induced by simian EBV-like viruses. The first is Cynomolgus-EBV-induced T-cell lymphomas in rabbits inoculated intravenously (77-90%) and orally (82- 89%) about 2 -5 months later. EBV-DNA was detected in peripheral blood by PCR since 2 days after oral inoculation while anti-EBV-VCA IgG was raised 3 weeks later. Rabbit lymphomas and their cell lines contained EBV-DNA and expressed EBV-encoded RNA-1 (EBER-1). Rabbit lymphomas and their cell lines contained EBV-DNA and expressed EBV-encoded RNA-1 (EBER-1). Rabbit lymphoma cell lines, some of which have specific chromosomal abnormality, showed tumorigenicity in nude mice. The second is the first and unique animal model for EBV-infected T-cell LPD with virus-associated hemophagocytic syndrome (VAHS) using rabbits infected with the baboon EBV-like herpesvirus, Herpesvirus papio (HVP). Rabbits inoculated intravenously with HVP-producing cells showed increased anti-EBV-VCA-IgG titers, and most (85%) subsequently died of fatal LPD and VAHS, with bleeding and hepatosplenomegaly, within a relatively short time (22-105 days). Peroral spray of cell-free HVP induced viral infection with seroconversion in 3 out of 5 rabbits, with 2 of the 3 infected rabbits dying of LPD with VAHS. Atypical T lymphocytes containing HVP-DNA and expressing EBER-1 were observed in many organs. Hemophagocytic histiocytosis was observed in the lymph nodes, spleen, bone marrow, and thymus. These rabbit models are also useful and inexpensive alternative experimental model systems for studying the biology and pathogenesis of EBV, and prophylactic and therapeutic regimens, especially in relation to human fatal EBV-related LPD and VAHS.
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