Comparalive epidemiological of study of viral zoonoses in Japan and Northern Eurasia

• Project/Area Number: 17255009
• Research Category: Grant-in-Aid for Scientific Research (A)
• Allocation Type: Single-year Grants
• Section: 海外学術
• Research Field: Applied veterinary science
• Research Institution: Hokkaido University
• Principal Investigator: TAKASHIMA Ikuo Hokkaido University, 大学院・獣医学研究科, 教授 (30002083)
• Co-Investigator(Kenkyū-buntansha): KARIWA Hiroaki 北海道大学, 大学院・獣医学研究科, 准教授 (70224714) ; MAEDA Akihiko 北海道大学, 大学院・獣医学研究科, 准教授 (70333359) ; ARIKAWA Jiro 北海道大学, 大学院・医学研究科, 教授 (10142704) ; 橋本 信夫 北海道大学, 名誉教授 (60082103)
• Project Period (FY): 2005 – 2008
• Project Status: Completed (Fiscal Year 2008)
• Budget Amount: ¥42,120,000 (Direct Cost: ¥32,400,000、Indirect Cost: ¥9,720,000); Fiscal Year 2008: ¥10,010,000 (Direct Cost: ¥7,700,000、Indirect Cost: ¥2,310,000); Fiscal Year 2007: ¥10,010,000 (Direct Cost: ¥7,700,000、Indirect Cost: ¥2,310,000); Fiscal Year 2006: ¥10,010,000 (Direct Cost: ¥7,700,000、Indirect Cost: ¥2,310,000); Fiscal Year 2005: ¥12,090,000 (Direct Cost: ¥9,300,000、Indirect Cost: ¥2,790,000)
• Keywords: ウイルス / 人獣共通感染症 / 疫学 / ウエストナイル熱 / ダニ媒介性脳炎 / ハンタウイルス感染症 / 北ユーラシア / 極東ロシア / 極東アジア

Research Abstract

近年、国内外で問題となっているウイルス性人獣共通感染症のうち、侵入または流行の危険性があり、重篤に経過し致死率が高いウエストナイル熱、ダニ媒介性脳炎およびハンタウイルス感染症について診断法を開発し、疫学調査を実施し、分離ウイルスの性状解析を行った。
ウエストナイルウイルスと日本脳炎ウイルスの遺伝子鑑別診断法としてリアルタイムPCR法を開発した。さらに準ウイルス粒子とウイルス様粒子を用いた血清学的な鑑別診断法を開発した。極東ロシアの野鳥の中和抗体を測定したところ、91羽中15羽(16.5%)にウエストナイル特異的な中和抗体が検出されたことから、極東ロシアの野鳥間にウエストナイルウイルスの流行していることが示唆された。
ダニ媒介性脳炎については準ウイルス粒子を用いたヒトおよび野ネズミ用の抗体検出ELISA を開発した。本ELISAを用いて国内各地の野ネズミ血清について抗体調査を実施したところ、島根県の野ネズミ58検体中2検体がダニ媒介性脳炎ウイルス特異抗体陽性となり、新しいウイルス汚染地が特定された。
ハンタウイルス感染症では、ウイルス核タンパクを対象にしたヒトおよび野ネズミの抗体検出ELISA および抗原検出ELISAを開発した。この抗体検出ELISAを用いてタイのレプトスピラ感染症を疑われた患者に、ハンタウイルス抗体陽性例を検出したため、ハンタウイルス感染症と症状の関連が示唆された。ロシアのボルガ川流域のサマラ市において、野ネズミの疫学調査を行い、流行中のウイルスはPuumala型のハンタウイルスであることを明らかにした。北海道の中川町と当別町においてエゾヤチネズミの疫学調査を行い、ハンタウイルスの野ネズミ集団内では、オスがメスよりも有意に高い感染率を示すことを明らかにした。

Research Products

• [Journal Article] Construction andapplication of chimeric virus-likeparticles of tick-borne encephalitisvirus and mosquito-borne Japaneseencephalitis virus. (2008)
  • Author(s): Yoshii K, Goto A, Kawakami K, Kariwa H, Takashima I
  • Journal Title: J. Gen. Virol 89 Pages: 200-211
  • Peer Reviewed
• [Journal Article] Development of a serotyping ELISA system for Thailand virus infection. (2008)
  • Author(s): Nakamura I, Yoshimatsu K, LeeBH, Okumura M, Taruishi M, Araki K, Kariwa H, Takashima I, Arikawa J
  • Journal Title: Arch. Virol 153 Pages: 1537-1542
  • Peer Reviewed
• [Journal Article] Genetic and antigenicanalyses of a Puumala virus isolate asa potential vaccine strain. (2008)
  • Author(s): Abu Daud NH, Kariwa H, Tkachenko E, Dzagurnova T, Medvedkina O,Tkachenko P, Ishizuka M, Seto T, Miyashita D, Sanada T, Nakauchi M,Yoshii K, Maeda A, Yoshimatsu K, ArikawaJ, Takashima I
  • Journal Title: Jpn. J. Vet. Res 56 Pages: 151-165
  • Peer Reviewed
• [Journal Article] A PCR-basedprotocol for generating West Nile virusreplicons (2008)
  • Author(s): Maeda J, Takagi H, Hashimoto S, Kurane I, Maeda A
  • Journal Title: J. Virol. Methods 148 Pages: 244-252
  • Peer Reviewed
• [Journal Article] Construction and application of chimeric virus-like particles of tick-borne encephalitis virus and mosquito-borne Japanese encephalitis virus (2008)
  • Author(s): Yoshii K, et.al.
  • Journal Title: J. Gen. Virol. 89 Pages: 200-211
  • Peer Reviewed
• [Journal Article] Genetic and antigenic analyses of a Puumala virus isolate as a potential vaccine strain (2008)
  • Author(s): Abu Daud NH, et.al.
  • Journal Title: Jpn. J. Vet. Res. 56 Pages: 151-165
  • Peer Reviewed
• [Journal Article] A PCR-based protocol for generating West Nile virus replicons (2008)
  • Author(s): Maeda J, et.al.
  • Journal Title: J. Virol. Methods 148 Pages: 244-252
  • Peer Reviewed
• [Journal Article] Development of a serotyping ELISA system for Thailand virus infection (2008)
  • Author(s): Nakamura I, et.al.
  • Journal Title: Arch. Virol 153 Pages: 1537-1542
  • Peer Reviewed
• [Journal Article] Molecular characterization of the E gene of dengue virus type I isolated in Guangdong Province, China, in 2006 (2008)
  • Author(s): Zheng K, et.al.
  • Journal Title: Epidemiology and Infection 37 Pages: 73-78
  • Peer Reviewed
• [Journal Article] Construction and application of cllnneric virus-like particles of tick-borne encephalitis virus and mosquito-borne Japanese encephalitis virus (2008)
  • Author(s): Yoshii K, et. al.
  • Journal Title: J. Gen. Virol 89 Pages: 200-211
  • Peer Reviewed
• [Journal Article] Mode of Infection of Hokkaido Virus(Genus Hantavirus) among Grey Red-Backed Voles, Myodes rufocanus, inHokkaido, Japan. (2007)
  • Author(s): Abu Daud NH, Kariwa, H, Tanikawa Y, Nakamura I, Seto T, Miyashita D, Yoshii K, Nakauchi M, Yoshimatsu K, Arikawa J, Takashima I
  • Journal Title: Microbiol. Immunol 21 Pages: 1081-1090
  • Peer Reviewed
• [Journal Article] Development ofserological assays for Thottapalayamvirus, an insectivore-borne Hantavirus (2007)
  • Author(s): Okumura M, Yoshimatsu K, Kumperasart S, Nakamura I, Ogino M, Taruishi M, Sungdee A, Pattamadilok S, Ibrahim IN, Erlina S, Agui T, YanagiharaR, Arikawa J
  • Journal Title: Clin. Vaccine. Immunol 14 Pages: 173-181
  • Peer Reviewed
• [Journal Article] Mode of Infection of Hokkaido virus(Genus Hantavirus)among Grey Red-Backed Voles, Myodes rufocanus, in Hokkaido, Japan (2007)
  • Author(s): Daud NHA, et. al.
  • Journal Title: Microbiol. Immunol 51 Pages: 1081-1090
  • Peer Reviewed
• [Journal Article] Hantavirus infection in East Asia (2007)
  • Author(s): Kariwa H, et. al.
  • Journal Title: Comp. Immunol. Microbiol .Inf. Dis. 30 Pages: 341-356
  • Peer Reviewed
• [Journal Article] A comparative epidemiological study of hantavirus infection in Japan and Far East Russia. (2007)
  • Author(s): Kariwa H, et al.
  • Journal Title: Jpn J. Vet. Res. 154 Pages: 145-161
• [Journal Article] Development of serological assays for Thottapalayam virus, an insectivore-borne hantavirus. (2007)
  • Author(s): Okumura M, et al.
  • Journal Title: Clin, Vac. Immunol. (In press)
• [Journal Article] Geographicaldistribution of hantaviruses inThailand and potential human healthsignificance of Thailand virus. (2006)
  • Author(s): Pattamadilok S, Lee BH, Kumperasart S, Yoshimatsu K, Okumura M, Nakamura I, Araki K, Khoprasert Y, Dangsupa P, Panlar P, Jandrig B, KrugerDH, Klempa B, Jakel T, Schmidt J, UlrichR, Kariwa H, Arikawa J
  • Journal Title: Am. J. Trop. Med. Hyg 75 Pages: 994-1002
  • Peer Reviewed
• [Journal Article] The kinetics ofproinflammatory cytokines in murineperitoneal macrophages infected withenvelope protein-glycosylated ornon-glycosylated West Nile virus (2006)
  • Author(s): Shirato K, Miyoshi H, KariwaH, Takashima I
  • Journal Title: Virus Res 121 Pages: 11-16
  • Peer Reviewed
• [Journal Article] Development of anenzyme-linked immunosorbent assay forserological diagnosis of tick-borneencephalitis using subviral particles (2006)
  • Author(s): Obara M, Yoshii K, Kawata T, Hayasaka D, Goto A, Mizutani T, Kariwa H, Takashima I
  • Journal Title: J. Virol. Methods 134 Pages: 55-60
  • Peer Reviewed
• [Journal Article] Development of an enzyme-linked immunosorbent assay for serological diagnosis of tick-borne encephalitis using subviral porticles. (2006)
  • Author(s): Obara M, et al.
  • Journal Title: J. Virol. Methods 134 Pages: 55-60
• [Journal Article] The kinetics of proinflammatory cytokines in murine peritoneal macrophages infected with envelope protein-glycosylated or non-glycosylated West Nile virus. (2006)
  • Author(s): Shirato K, et al.
  • Journal Title: Virus Res. 121 Pages: 11-16
• [Journal Article] Soochong virus : an antigenically and genetically distinct hantavirus isolated from Apodemus peninsulae in Korea. (2006)
  • Author(s): Baek L J, et al.
  • Journal Title: J. Med. Virol. 78 Pages: 290-297
• [Journal Article] Detection of West Nilevirus and Japanese encephalitis virususing real-time PCR with a probe commonto both viruses (2005)
  • Author(s): Shirato K, Miyoshi H, Kariwa H, Takashima I
  • Journal Title: J. Virol. Methods 126 Pages: 119-125
  • Peer Reviewed
• [Journal Article] Role of the N-linked glycans of prM and E envelope proteins in tick-borne encephalitis virus particle secretion. (2005)
  • Author(s): Goto A, et al.
  • Journal Title: Vaccine 23 Pages: 3043-3052
• [Journal Article] Detection of West Nile virus and Japanese encephalitis virus using real-time PCR with a probe common to both viruses. (2005)
  • Author(s): Shiraro K, et al.
  • Journal Title: J.Virol.Methods 126 Pages: 119-125
• [Journal Article] Packaging the replicon RNA of the Far-Eastern subtype of tick-borne encephalitis virus into single-round infectious particles : development of a heterologous gene delivery system. (2005)
  • Author(s): Yoshii K, et al.
  • Journal Title: Vaccine 23 Pages: 3946-3956
• [Journal Article] Nucleocapsid protein of cell culture-adapted Seoul virus strain 80-39 : analysis of its encoding sequence, expression in yeast and immuno-reactivity. (2005)
  • Author(s): Schmidt K, et al.
  • Journal Title: Virus Gene 30 Pages: 37-48
• [Journal Article] 日本と極東ロシアのダニ媒介性脳炎ウイルスの系統解析と病原性 (2005)
  • Author(s): 高島郁夫 他
  • Journal Title: ウイルス 55 Pages: 35-44
  • NAID: 10016449362
• [Presentation] 多種類のハンタウイルス血清型の検出が可能な抗原検出法の開発 : 第56回日本ウイルス学界学術集会 (2008)
  • Author(s): 真田崇弘, ら
  • Organizer: 第56回日本ウイルス学会学術集会
  • Place of Presentation: 岡山コンベンションセンター
  • Year and Date: 2008-10-27
• [Presentation] Genetic and antigenic characterization of Puumala virus strain DTK / Ufa-97 isolated from a patient of hemorrhagic fever with renal syndrome (2008)
  • Author(s): Nur Hardy Abu Daud, ら
  • Organizer: 第56回日本ウイルス学会学術集会
  • Place of Presentation: 岡山コンベンションセンター
  • Year and Date: 2008-10-27
• [Presentation] ウイルス様粒子を用いたウエストナイルウイルスと日本脳炎ウイルス感染症との鑑別中和試験法の開発 : トガ・フラビ・ペスチウイルス研究会 (2008)
  • Author(s): 前田秋彦, ら
  • Organizer: 第56回日本ウイルス学会学術集会
  • Place of Presentation: 岡山コンベンションセンター
  • Year and Date: 2008-10-27
• [Presentation] ウエストナイルウイルスのE蛋白上糖鎖付加がウイルス増殖に与える影響 (2008)
  • Author(s): 村田亮, ら
  • Organizer: 第56回日本ウイルス学会学術集会
  • Place of Presentation: 岡山コンベンションセンター
  • Year and Date: 2008-10-26
• [Presentation] ダニ媒介性脳炎ウイルスの中空ウイルス様粒子のワクチンへの応用 (2008)
  • Author(s): 大森優紀, ら
  • Organizer: 第56回日本ウイルス学会学術集会
  • Place of Presentation: 岡山コンベンションセンター
  • Year and Date: 2008-10-26
• [Presentation] ウエストナイルウイルスと日本脳炎ウイルスの鑑別中和試験法の開発 (2008)
  • Author(s): 前田潤子, ら
  • Organizer: 第146回日本獣医学会学術集会
  • Place of Presentation: 宮崎ワールドコンベンションセンター
  • Year and Date: 2008-09-24
• [Presentation] ウエストナイル熱の血清診断法の評価と極東ロシアにおける疫学調査 (2008)
  • Author(s): 村田亮, ら
  • Organizer: 第146回日本獣医学会学術集会
  • Place of Presentation: 宮崎ワールドコンベンションセンター
  • Year and Date: 2008-09-24
• [Presentation] 多種類のハンタウイルス血清型の検出が可能な抗原検出法の開発 (2008)
  • Author(s): 真田崇弘, ら
  • Organizer: 第146回日本獣医学会学術集会
  • Place of Presentation: 宮崎ワールドコンベンションセンター
  • Year and Date: 2008-09-24
• [Presentation] ウイルス様粒子を用いたダニ媒介性脳炎の新たな診断法の開発 (2008)
  • Author(s): 千葉裕美子, ら
  • Organizer: 第146回日本獣医学会学術集会
  • Place of Presentation: 宮崎ワールドコンベンションセンター
  • Year and Date: 2008-09-24
• [Presentation] ダニ媒介性脳炎ウイルスの中空ウイルス様粒子のワクチンへの応用 (2008)
  • Author(s): 大森優紀, ら
  • Organizer: 第146回日本獣医学会学術集会
  • Place of Presentation: 宮崎ワールドコンベンションセンター
  • Year and Date: 2008-09-24
• [Presentation] モノクローナル抗体を用いた食中目由来ハンタウイルスThottapalayamウイルスの抗原性の解析 (2008)
  • Author(s): Erdenensaikhan T, ら
  • Organizer: 第146回日本獣医学会
  • Place of Presentation: 宮崎ワールドコンベンションセンター
  • Year and Date: 2008-09-24
• [Presentation] A seroepidemiological studyof a West Nile virus infection amongwild birds in Far East Russia and therelationship between glycosylation ofthe virus (2008)
  • Author(s): Takashima I, Murata R, Hashiguchi K, Kariwa H
  • Organizer: XIVth InternationalCongress of Virology
  • Place of Presentation: Istanbul
  • Year and Date: 2008-08-12
• [Presentation] Epidemiological investigation ofhantavirus infection in rodents from Mexico (2008)
  • Author(s): Kariwa H, Miyashita D, Hernandez CS, Romero-Almaraz ML, Ramos C, Seto T, Murata R, Abu Daud NH, Ishizuka M, Nakauchi M, Yoshii K, Yoshimatsu K, Arikawa J, Takashima I
  • Organizer: XIVth International Congress of Virology
  • Place of Presentation: Istanbul
  • Year and Date: 2008-08-12
• [Presentation] A seroepidemiological study of a West Nile Virus infection among wild birds in Far East Russia and the relationship between glycosylation of the virus (2008)
  • Author(s): Takashima I, et.al.
  • Organizer: XIVth International Congress of Virology
  • Place of Presentation: Istanbul Concvention And Exhibition Center
  • Year and Date: 2008-08-12
• [Presentation] Epidemiological investigation of hantavirus infection in rodents from Mexico (2008)
  • Author(s): Kariwa H, et.al.
  • Organizer: XIVth International Congress of Virology
  • Place of Presentation: Istanbul Concvention And Exhibition Center
  • Year and Date: 2008-08-12
• [Presentation] Antigenic profile of thottapalayam virus and development of a serodiagnostic assay (2008)
  • Author(s): Okumura M, et.al.
  • Organizer: XIVth International Congress of Virology
  • Place of Presentation: Istanbul Concvention And Exhibition Center
  • Year and Date: 2008-08-12
• [Presentation] Epidemiological study on Flavivirusesin Guangdong province, China (2008)
  • Author(s): Maeda A, Maeda J, Ma H, Ke C -W, TakagiH, Takashima I, Kurane I
  • Organizer: 42nd Joint Viral Diseases Panels Meeting, US-Japan Cooperative Medical Science Program
  • Place of Presentation: Nagasaki
  • Year and Date: 2008-05-26
• [Presentation] ロシアのボルガ川流域におけるハンタウイルス感染症の疫学的研究 (2007)
  • Author(s): 瀬戸隆弘
  • Organizer: 第55回日本ウイルス学会
  • Place of Presentation: 札幌コンベンションセンター,札幌市
  • Year and Date: 2007-10-22
• [Presentation] Viral envelope glycosylation is amolecular determinant of theneuroinvasiveness of the New Yorkstrain of West Nile virus (2005)
  • Author(s): Takashima I, Shirato K, Goto A, Kariwa H
  • Organizer: 13^<th> International Congress of Virology
  • Place of Presentation: San Francisco, U.S.A.
  • Year and Date: 2005-07-26
• [Presentation] Genetic andantigenic characterization ofhantavirus isolates in Amur and FarEast genotypes (2005)
  • Author(s): Kariwa H, Lokugamage K, Lokugamage N, Miyamoto H, Iwasa MA, Hagiya T, ArakiK, Tachi A, Mizutani T, Yoshimatsu K, Arikawa J, Takashima I
  • Organizer: 13^<th> InternationalCongress of Virology
  • Place of Presentation: San Francisco, U.S.A.
  • Year and Date: 2005-07-26
• [Book] Differential sero-diagnosis offlaviviruses using sub-viralparticles and virus-like particles (2009)
  • Author(s): Maeda A, Maeda J, Murata R, Akiyama M, Kariwa H, Takashima I
  • Publisher: Animal Viruses. Ed. Maeda A (In press)
• [Book] Epidemiologicalstudy of Flaviviruses in Guangdongprovince, China, 2005-2007 (2009)
  • Author(s): Ma H, Ke C -W, Maeda J, Takashima I, Kurane I, Maeda A
  • Publisher: Animal Viruses. Ed. Maeda A (In press)
• [Book] Differential sero-diagnosis of flaviviruses using subviral particles and virus-like particles. in Animal Viruses (2009)
  • Author(s): Maeda A., et.al.
  • Total Pages: 14
  • Publisher: Research Signpost / Transworld Research Network
• [Book] Epidemiological study of Flaviviruses in Guangdong Province, China, 2005-2007 (2009)
  • Author(s): Ma H, Ke C-W, et.al.
  • Total Pages: 14
  • Publisher: Research Signpost / Transworld Research Network