1993 Fiscal Year Annual Research Report

遺伝子工学的および臨床生化学的手法での腎症候性出血熱疾患モデルマウスの病態の解析

Research Project

Project/Area Number	03558009
Research Institution	Hokkaido University
Principal Investigator	有川二郎北海道大学, 免疫科学研究所, 助教授 (10142704)
Co-Investigator(Kenkyū-buntansha)	伊勢川裕二大阪大学, 微生物病研究所, 助手 (20184583) 石原智明酪農学園大学, 獣医学科, 教授 (90082172) 吉松組子北海道大学, 免疫科学研究所, 教務職員 (90220722) 板倉智敏北海道大学, 獣医学部, 教授 (30021695) 橋本信夫北海道大学, 獣医学部, 教授 (60082103)
Keywords	腎症候性出血熱 / ハンタウイルス / 動物モデル / SCIDマウス / PCR / ウイルス感染 / 動物実験 / 臨床生化学
Research Abstract	腎症候性出血熱の疾患モデルの作製ならびにその病態の解析を目的として研究を行い以下のような成績を得た 1.腎症候性出血熱ウイルスSR-11株およびHantaan76-118株感染SCIDマウスにおいて、脾臓では接種4日後から、脳、肺、腎臓からは接種後14日目以降、血清と血球分画からは10日目以降、いずれも継続してウイルスが分離され、接種35日目には発症・死亡することが判明した。 2.Hantaan76-118株感染後21日後のSCIDマウスに正常BALB/cマウス由来の脾臓細胞を移入すると、移入4日目以降、抗Hantaan virus抗体の急激な出現と同時に血中BUN値の顕著な上昇が認められ、感染腎臓組織への免疫反応が機能障害を引き起こしていると考えられた。しかし、明瞭な病理組織学的変性の出現ならびに免疫複合体の沈着は確認されていない。 3.RT-PCRとNested-PCR法を組み合わせることによって感染動物臓器からHantaan virusゲノム高感度な検出系を確立した。本法によるゲノム検出には血球分画が最適で、検出感度はウイルス分離法と概ね同等であった。 4.北欧で人に軽症の腎症候性出血熱を引き起こすPuumala virusをSCIDマウスに接種したところ、全例36日間以上無症状で耐過した。その後、正常マウス由来脾臓細胞を移入すると抗体の陽転が観察され感染が確認された。このため、本株はマウスに対して弱毒と考えられた。今後、感染SCIDマウスへの免疫細胞の移入実験後の病態について、各種サイトカイン類の変動も含めて検討を加える予定である。

Research Products

(21 results)

All Other

All Publications (21 results)

[Publications] Yao,J.-S.: "Antibody-dependent enhancement of hantavirus ifection in macrophge cell lines." Archives of Virology. 122. 107-118 (1991)
[Publications] Kobayashi,K.: "Renal lesions in rats infected with Rattus serotype hantavirus(SR-11 strain)." Journal of Veterinary Medicine. B38. 657-664 (1991)
[Publications] Mori,F.: "Pathological studies on central nervous tissues of rats infected with Rattus serotype hantaviruses." Journal of Veterinary Medicine. B38. 665-672 (1991)
[Publications] Kawamura,K.: "Susceptibility of laboratory and wild rodents to Rattus or Apodemus-type hantaviruses." Acta Virologica. 35. 54-63 (1991)
[Publications] 苅和宏明: "ドブネズミにおける腎症候性出血熱ウイルス感染の疫学的研究" 北海道獣医師会誌. 35. 69-74 (1991)
[Publications] Arikawa,J.: "Protective role of antigeni sites on the envelope protein of Hantaan virus defined by monoclonal antibodies." Archives of Virology. 126. 271-281 (1992)
[Publications] Kariwa,H.: "Development and application of protein G antibody assay for the detection of antibody to hantavirus." Journal of Virological Methods. 37. 345-354 (1992)
[Publications] Yao,J.-S.: "Effect of neutralizing monoclonal antibodies on Hantaan virus infection of the macrophage P388D1 cell line." Japanese Journal of Veterinary Research. 40. 87-97 (1992)
[Publications] Azuma,I.: "Stimulation of host-defense mechanism with synthetic adjuvants and recombinant cytokines against viral infection in mice." Microbial Infections. 19. 253-263 (1992)
[Publications] Isegawa,Y.: "Selective amplification of cDNA sequence from total RNA by cassetteligation mediated polymerase chain reaction(PCR):Application to sequencing 6.5kb genome segment of hantavirus strain B-1." Molecular and Cellular Probes. 6. 467-475 (1992)
[Publications] Arikawa,J.: "Protective role of antigenic sites on the envelope protein of Hantaan virus defined by monoclonal antibodies." Archives of Virology. 126. 271-281 (1992)
[Publications] 大島淳: "PCR法による腎症候性出血熱ウイルスHantaan株の微量検出法" 日本臨床. 50. 305-309 (1992)
[Publications] Ishihara,C.: "Anti-viral activity of sulfated chitin derivatives against Friend Leukemia and herpes simplex type-1 viruses." Vaccine. 11. 670-673 (1993)
[Publications] Yoshimatsu,K.: "Protective immunity of Hantaan virus nucleocapsid protein studied using the baculovirus-expressed proteins." Archives of Virology. 130. 365-376 (1993)
[Publications] Yoo,Y.-C.: "Comparison of virulence between Seoul type virus strain SR-11 and Hantaan type virus strain 76-118 of hantaviruses in suckling mice." Microbiology and Immunology. 37. 557-562 (1993)
[Publications] Yoshimatsu,K.: "Application of recombinant baculovirus expressed hantavirus nucleocapsid protein as a diagnostic antigen inIFA test" Journal of Veterinary Medical Science. 55. 1047-1050 (1993)
[Publications] 有川二郎: "特集腎症候性出血熱(HFRS);最近の話題,免疫学的・診断学的立場から." アニテックス. 5. 277-281 (1993)
[Publications] 伊勢川裕二: "特集腎症候性出血熱(HFRS);最近の話題,腎症候性出血熱ウイルス." アニテックス. 5. 273-276 (1993)
[Publications] Arikawa,J.: "Epizootiological studies of hantavirus infection among urban rats in Hokkaido,Japan" Journal of Veterinary Medical Science. 56. 27-32 (1994)
[Publications] Kariwa,H.: "Enhancement of infectivity of hantavirus in cell culture by centrifugation." Journal of Virological Method. (in press). (1994)
[Publications] Kariwa,H.: "Comparison of nucleotide sequences of M genome segments among Seoul virus strains isolated from Eastern Asia." Virus Research. (in press). (1994)

1993 Fiscal Year Annual Research Report

遺伝子工学的および臨床生化学的手法での腎症候性出血熱疾患モデルマウスの病態の解析

Principal Investigator

有川 二郎 北海道大学, 免疫科学研究所, 助教授 (10142704)

Research Products

[Publications] Yao,J.-S.: "Antibody-dependent enhancement of hantavirus ifection in macrophge cell lines." Archives of Virology. 122. 107-118 (1991)

[Publications] Kobayashi,K.: "Renal lesions in rats infected with Rattus serotype hantavirus(SR-11 strain)." Journal of Veterinary Medicine. B38. 657-664 (1991)

[Publications] Mori,F.: "Pathological studies on central nervous tissues of rats infected with Rattus serotype hantaviruses." Journal of Veterinary Medicine. B38. 665-672 (1991)

[Publications] Kawamura,K.: "Susceptibility of laboratory and wild rodents to Rattus or Apodemus-type hantaviruses." Acta Virologica. 35. 54-63 (1991)

[Publications] 苅和宏明: "ドブネズミにおける腎症候性出血熱ウイルス感染の疫学的研究" 北海道獣医師会誌. 35. 69-74 (1991)

[Publications] Arikawa,J.: "Protective role of antigeni sites on the envelope protein of Hantaan virus defined by monoclonal antibodies." Archives of Virology. 126. 271-281 (1992)

[Publications] Kariwa,H.: "Development and application of protein G antibody assay for the detection of antibody to hantavirus." Journal of Virological Methods. 37. 345-354 (1992)

[Publications] Yao,J.-S.: "Effect of neutralizing monoclonal antibodies on Hantaan virus infection of the macrophage P388D1 cell line." Japanese Journal of Veterinary Research. 40. 87-97 (1992)

[Publications] Azuma,I.: "Stimulation of host-defense mechanism with synthetic adjuvants and recombinant cytokines against viral infection in mice." Microbial Infections. 19. 253-263 (1992)

[Publications] Isegawa,Y.: "Selective amplification of cDNA sequence from total RNA by cassetteligation mediated polymerase chain reaction(PCR):Application to sequencing 6.5kb genome segment of hantavirus strain B-1." Molecular and Cellular Probes. 6. 467-475 (1992)

[Publications] Arikawa,J.: "Protective role of antigenic sites on the envelope protein of Hantaan virus defined by monoclonal antibodies." Archives of Virology. 126. 271-281 (1992)

[Publications] 大島淳: "PCR法による腎症候性出血熱ウイルスHantaan株の微量検出法" 日本臨床. 50. 305-309 (1992)

[Publications] Ishihara,C.: "Anti-viral activity of sulfated chitin derivatives against Friend Leukemia and herpes simplex type-1 viruses." Vaccine. 11. 670-673 (1993)

[Publications] Yoshimatsu,K.: "Protective immunity of Hantaan virus nucleocapsid protein studied using the baculovirus-expressed proteins." Archives of Virology. 130. 365-376 (1993)

[Publications] Yoo,Y.-C.: "Comparison of virulence between Seoul type virus strain SR-11 and Hantaan type virus strain 76-118 of hantaviruses in suckling mice." Microbiology and Immunology. 37. 557-562 (1993)

[Publications] Yoshimatsu,K.: "Application of recombinant baculovirus expressed hantavirus nucleocapsid protein as a diagnostic antigen inIFA test" Journal of Veterinary Medical Science. 55. 1047-1050 (1993)

[Publications] 有川二郎: "特集腎症候性出血熱(HFRS);最近の話題,免疫学的・診断学的立場から." アニテックス. 5. 277-281 (1993)

[Publications] 伊勢川裕二: "特集腎症候性出血熱(HFRS);最近の話題,腎症候性出血熱ウイルス." アニテックス. 5. 273-276 (1993)

[Publications] Arikawa,J.: "Epizootiological studies of hantavirus infection among urban rats in Hokkaido,Japan" Journal of Veterinary Medical Science. 56. 27-32 (1994)

[Publications] Kariwa,H.: "Enhancement of infectivity of hantavirus in cell culture by centrifugation." Journal of Virological Method. (in press). (1994)

[Publications] Kariwa,H.: "Comparison of nucleotide sequences of M genome segments among Seoul virus strains isolated from Eastern Asia." Virus Research. (in press). (1994)

有川二郎北海道大学, 免疫科学研究所, 助教授 (10142704)