Establishment of novel preventive/therapeutic measures and demonstration of a mechanism of neural spread of pathogens in neurotropic zoonotic diseases

• Project/Area Number: 19380171
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Applied veterinary science
• Research Institution: Hokkaido University
• Principal Investigator: UMEMURA Takashi Hokkaido University, 大学院・獣医学研究科, 教授 (00151936)
• Co-Investigator(Kenkyū-buntansha): PARK Chon-ho 北里大学, 獣医畜産学部, 准教授 (50383550) ; KIDA Hiroshi 北海道大学, 大学院・獣医学研究科, 教授 (10109506)
• Project Period (FY): 2007 – 2009
• Project Status: Completed (Fiscal Year 2009)
• Budget Amount: ¥19,890,000 (Direct Cost: ¥15,300,000、Indirect Cost: ¥4,590,000); Fiscal Year 2009: ¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000); Fiscal Year 2008: ¥8,840,000 (Direct Cost: ¥6,800,000、Indirect Cost: ¥2,040,000); Fiscal Year 2007: ¥7,150,000 (Direct Cost: ¥5,500,000、Indirect Cost: ¥1,650,000)
• Keywords: 狂犬病 / 鞘内免疫 / インフルエンザウイルス / 小児脳症 / オーエスキー病 / 血球凝集性脳脊髄炎ウイルス / インフルエンザ脳症 / 野兎病 / 人獣共通感染症 / 脳内免疫 / LPS / 経神経伝播 / ワクチン / 人畜共通感染症

Research Abstract

Specific antibodies detected in cerebrospinal fluid by intrathecal vaccination (vaccination by an inoculating antigen into subarachnoidal space) were produced de novo in the brain. Intrathecal vaccination completely prevented clinical signs and death of mice inoculated with rabies or pseudorabies viruses. Eighty percent of the mice intrathecally vaccinated and inoculated rabies virus directly into the brain survived, and this result suggested that the intrathecal vaccination was applicable for the treatment of rabid animals and humans. Our novel murine model of influenzal encephalopathy of childhood suggested hypercytokinemia triggered by influenza virus infection and/or a duplication of influenza virus infection and endotoxemia might be the cause(s) of the disease.

Research Products

• [Journal Article] Influenza A virus infection enhances lipopolysaccaride-induced encephalopathy in neonatal mice. (2010)
  • Author(s): Tanaka T, Sunden Y, Sakoda Y, Kida H, Ochiai K, Umemura T
  • Journal Title: J Neurovirol (in press)(Epub ahead of print)
  • Peer Reviewed
• [Journal Article] Lesions of the central nervous system induced by intracerebral inoculation of BALB/c mice with rabies virus (CVS-11). (2010)
  • Author(s): Kojima D, Park CH, Tsujikawa S, Kohara K, Hatai H, Oyamada T, Noguchi A, Inoue S
  • Journal Title: J Vet Med Sci (in press)(Epub ahead of print)
  • Peer Reviewed
• [Journal Article] Glycosylation of the West Nile virus envelope protein increases in vivo and in vitro viral multiplication in birds. (2010)
  • Author(s): Murata R, Eshita Y, Maeda A, Maeda J, Akita S, Yanaka T, Yoshii K, Kariwa H, Umemura T, Takashima I
  • Journal Title: Am J Trop Med Hyg 82 Pages: 696-704
  • Peer Reviewed
• [Journal Article] 野兎病菌に自然感染したトウホクノウサギ(Lepus brachyurus angustidens)の症例-野生動物の病理解剖の意義と感染リスク- (2010)
  • Author(s): 朴天錆, 中西中, 畑井仁, 小山田敏文, 佐藤久聡, 進藤順治, 藤田修, 堀田明豊, 井上智, 棚林清
  • Journal Title: 獣医畜産新報 63(3) Pages: 197-200
  • Peer Reviewed
• [Journal Article] Influenza A virus infection enhances lipopolysaccaride-induced encephalopathy in neonatal mice (2010)
  • Author(s): Tanaka T, Sunden Y, Sakoda Y, Kida H, Ochiai K, Umemura T
  • Journal Title: Journal of Neurovirology (印刷中, 印刷中4)
  • Peer Reviewed
• [Journal Article] Glycosylation of the West Nile virus envelope protein increases in vivo and in vitro viral multiplication in birds (2010)
  • Author(s): Murata R, Eshita Y, Maeda A, Maeda J, Akita S, Yanaka T, Yoshii K, Kariwa H, Umemura T, Takashima
  • Journal Title: American Journal of Tropical Medicine and Hygien (印刷中)
  • Peer Reviewed
• [Journal Article] Effective prevention against rabies by intracerebral immunizaton in mice. (2009)
  • Author(s): Shin JH, Sakoda Y, Yano S, Ochiai K, Kida H, Umemura T
  • Journal Title: J Vet Med Sci 71 Pages: 1331-1336
• [Journal Article] Pathology of the Spinal Cord of C57BL/6J Mice Infected with Rabies Virus (CVS-11 Strain). (2009)
  • Author(s): Kojima D, Park CH, Sato Y, Inoue S, Noguchi A, Oyamada T
  • Journal Title: J Vet Med Sci 71(3) Pages: 319-324
  • Peer Reviewed
• [Journal Article] Pathological and microbiological studies of Japanese hare (Lepus braehyurus angustidens) naturally infected with Francisella tularensissubsp. holarctica. (2009)
  • Author(s): Park CH, Nakanishi A, Hatai H, Kojima D, Oyamada T, Sato H, Kudo N, Shindo J, Fujita O, Hotta A, Inoue S, Tanabayashi K
  • Journal Title: J Vet Med Sci 71 Pages: 1629-1635
  • Peer Reviewed
• [Journal Article] Infectious entry of equine herpesvirus-1 into host cells through different endocytic pathways. (2009)
  • Author(s): Hasebe R, Sasaki M, Sawa H, Wada R, Umemura T, Kimura T
  • Journal Title: Virology 393 Pages: 198-209
• [Journal Article] Propagation of swine hemagglutinating encephalomyelitis virus and pseudorabies virus in dorsal root ganglia cells. (2009)
  • Author(s): Hara Y, Hasebe R, Sunden Y, Ochiai K, Honda E, Sakoda Y, Umemura T
  • Journal Title: J Vet Med Sci 71 Pages: 595-601
  • NAID: 130000134370
  • Peer Reviewed
• [Journal Article] In vitro propagation of rabies virus in mouse dorsal root ganglion cells. (2009)
  • Author(s): Hara Y, Sunden Y, Ochiai K, Umemura T
  • Journal Title: Jpn J Vet Res 56 Pages: 181-188
  • Peer Reviewed
• [Journal Article] Effective prevention against rabies by intracerebral immunizaton in mice. (2009)
  • Author(s): Shin JH, Sakoda Y, Yano S, Ochiai K, Kida H, Umemura T
  • Journal Title: Journal of Veterinary Medical Science 71 Pages: 1331-1336
  • Peer Reviewed
• [Journal Article] Infectious entry of equine herpesvirus-1 into host cells through different endocytic pathways (2009)
  • Author(s): Hasebe R, Sasaki M, Sawa H, Wada R, Umemura T, Kimura T
  • Journal Title: Virology 393 Pages: 198-209
  • Peer Reviewed
• [Journal Article] Propagation of swine hemagglutinating encephalomyelitis virus and pseudorabies virus in dorsal root ganglia cells (2009)
  • Author(s): Hara Y, Hasebe R, Sunden Y, Ochiai K, Honda E, Sakoda Y, Umemura T
  • Journal Title: Journal of Veterinary Medical Science 71 Pages: 181-189
  • NAID: 130000134370
  • Peer Reviewed
• [Journal Article] In vitro propagation of rabies virus in mouse dorsal root ganglion cells (2009)
  • Author(s): Hara Y, Sunden Y, Ochiai K, Umemura T
  • Journal Title: Japanese Journal of Veterinary Research 56 Pages: 181-188
  • Peer Reviewed
• [Journal Article] Lesions of the central nervous system induced by intracerebral inoculation of BALB/c mice with rabies virus (CVS-11) (2009)
  • Author(s): Kojima D, Park CH, Tsujikawa S, Kohara K, Hatai H, Oyamada T, Noguchi A, Inoue S
  • Journal Title: Journal of Veterinary Medical Science (印刷中)
  • Peer Reviewed
• [Journal Article] Pathological and microbiological studies of Japanese hare (Lepus brachyurus angustidens) naturally infected with Francisella tularensis subsp. holarctica (2009)
  • Author(s): Park CH, Nakanishi A, Hatai H, Kojima D, Oyamada T, Sato H, Kudo N, Shindo J, Fujita O, Hotta A, Inoue S, Tanabayashi K
  • Journal Title: Journal of Veterinary Medical Science 71 Pages: 1629-1635
  • Peer Reviewed
• [Journal Article] Pathology of the spinal cord of C57BL/6J mice infected with rabies virus(CVS-11 strain) (2009)
  • Author(s): Kojima D, Park CH, Sato Y, Inoue S, Noguchi A, Oyamada T
  • Journal Title: Journal of Veterinary Medical Science 71 Pages: 319-324
  • Peer Reviewed
• [Journal Article] In vitro propagation of rabies virus in mouse dorsal root ganglion cells (2009)
  • Author(s): Hara Y
  • Journal Title: Japanese Journal of Veterinary Research 56 Pages: 181-188
  • Peer Reviewed
• [Journal Article] Comparison of antibody titers in rabbits following immunization with inactivated influenza virus via subarachnoidal or subcutaneous route. (2007)
  • Author(s): Shin JH, Sakoda Y, Kida H, Kim JH, Ochiai K, Umemura T
  • Journal Title: J Vet Med Sci 69 Pages: 1167-1169
  • NAID: 110006452654
  • Peer Reviewed
• [Journal Article] Identification of DDX1 as a JC virus transcriptional control region-binding protein. (2007)
  • Author(s): Sunden Y, Samba S, Suzuki T, Okada Y, Orba Y, Nagashima K, Umemura T, Sawa H
  • Journal Title: Microbial Immunol 51 Pages: 327-337
  • NAID: 10020281217
  • Peer Reviewed
• [Journal Article] DDX1 promotes proliferation of JC virus through transactivation of its promoter. (2007)
  • Author(s): Sunden Y, Samba S, Suzuki T, Okada Y, Orba Y, Nagashima K, Umemura T, Sawa H
  • Journal Title: Microbiol Immunol 51 Pages: 339-347
  • NAID: 10020281242
• [Journal Article] Comparison of antibody titers in rabbits following immunization with in activated influenza virus via subarachnoidal or subcutaneous route (2007)
  • Author(s): Shin JH
  • Journal Title: Journal of Veterinary Medical Science 69 Pages: 1167-1169
  • Peer Reviewed
• [Presentation] インフルエンザウイルス感染COX-2欠損乳のみマウスの実験病理学的研究 (2010)
  • Author(s): 田中智久、秋田沙希、寸田祐嗣、落合謙爾、梅村孝司
  • Organizer: 第149回日本獣医学会
  • Place of Presentation: 日本獣医科学大学、東京
• [Presentation] Suppression of rabies virus propagation in mice brain by intracerebral immunization of inactivated virus (2009)
  • Author(s): Sunden Y, Yano S, Ochiai K, Umemura T
  • Organizer: 4^<th> Meeting of Asian Society of Veterinary Pathologists
  • Place of Presentation: Bangkok, Thai
  • Year and Date: 2009-11-19
• [Presentation] Mouse model of influenza virus-associated encephalopathy of childhood (2009)
  • Author(s): Tanaka T, Sunden Y, Tanoue G, Ochiai K, Umemura T
  • Organizer: 27^<th> Meeting of the European Society of Veterinary Pathology
  • Place of Presentation: Krakow, Poland
  • Year and Date: 2009-09-10
• [Presentation] The immune response in mice following intra-cerebral vaccination against pseudorabies virus (2009)
  • Author(s): Lee HK, Sunden Y, Ochiai K, Umemrua T
  • Organizer: 27^<th> Meeting of the European Society of Veterinary Pathology
  • Place of Presentation: Krakow, Poland
  • Year and Date: 2009-09-10
• [Presentation] Suppression of rabies virus propagation in mice brain by intracerebral immunization of inactivated virus. (2009)
  • Author(s): Umemura T
  • Organizer: 4th Meeting of Asian Society of Veterinary Pathologists
  • Place of Presentation: Bangkok, Thailand(invited speaker)
• [Presentation] Mouse model of influenza virus-associated encephalopathy of childhood. (2009)
  • Author(s): Tanaka T, Sunden Y, Tanoue G, Ochiai K, Sakoda Y, Kida H, Umemura T
  • Organizer: 27^<th> Meeting of the European Society of Veterinary Pathology and of the European College of Veterinary Pathologists
  • Place of Presentation: Krakow, Poland
• [Presentation] The immune response in mice following intra-cerebral vaccination against pseudorabies virus (2009)
  • Author(s): Lee HK, Sunden Y, Ochiai K, Umemura T
  • Organizer: 27^<th> Meeting of the European Society of Veterinary Pathology and of the European College of Veterinary Pathologists
  • Place of Presentation: Krakow, Poland
• [Presentation] 鞘内免疫による狂犬病治療効果の基礎検討 (2008)
  • Author(s): 寸田祐嗣
  • Organizer: 第56回日本ウイルス学会学術集会
  • Place of Presentation: 岡山市(岡山ポートランド)
  • Year and Date: 2008-10-27
• [Presentation] マウスを用いた小児インフルエンザ脳症の再現実験 : LPS投与の影響 (2008)
  • Author(s): 田中智久
  • Organizer: 第146回日本獣医学会学術集会
  • Place of Presentation: 宮崎市(シーガイア)
  • Year and Date: 2008-09-24
• [Presentation] マウスを用いた小児インフルエンザ脳症の再現実験: LPS投与の影響 (2008)
  • Author(s): 田中智久、寸田祐嗣、田上銀平、迫田義博、落合謙爾、喜田宏、梅村孝司
  • Organizer: 第56回日本ウイルス学会
  • Place of Presentation: 岡山コンベンションセンター
• [Presentation] H5N1型インフルエンザウイルスに感染した野生オオハクチョウの病理学的検索 (2008)
  • Author(s): 田中智久、寸田祐嗣、岡松正敏、迫田義博、落合謙爾、梅村孝司
  • Organizer: 第146回日本獣医学会
  • Place of Presentation: シーガイア、宮崎
• [Presentation] 鞘内免疫法による狂犬病治療効果の基礎研究 (2008)
  • Author(s): 寸田祐嗣、矢野志織、落合謙爾、梅村孝司
  • Organizer: 第145回日本獣医学会
  • Place of Presentation: 麻布大学、東京