Elucidation of the pathogenesis of dengue fever and dengue hemorrhagic fever based on viral and immunological analysis

• Project/Area Number: 22390093
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Virology
• Research Institution: National Institute of Infectious Diseases
• Principal Investigator: KURANE Ichiro 国立感染症研究所, 副所長 (90278656)
• Co-Investigator(Kenkyū-buntansha): TAKASAKI Tomohiko 国立感染症研究所, ウイルス第一部室長 (20221351) ; MATSUTANI Takaji 和歌山県立医科大学, 医学部, 講師 (70372290) ; SUZUKI Ryuji 独立行政法人国立病院機構相模原病院臨床研究センター, 室長 (70373470)
• Project Period (FY): 2010 – 2012
• Project Status: Completed (Fiscal Year 2012)
• Budget Amount: ¥16,640,000 (Direct Cost: ¥12,800,000、Indirect Cost: ¥3,840,000); Fiscal Year 2012: ¥2,860,000 (Direct Cost: ¥2,200,000、Indirect Cost: ¥660,000); Fiscal Year 2011: ¥6,370,000 (Direct Cost: ¥4,900,000、Indirect Cost: ¥1,470,000); Fiscal Year 2010: ¥7,410,000 (Direct Cost: ¥5,700,000、Indirect Cost: ¥1,710,000)
• Keywords: ウイルス / 感染症 / 免疫学 / デングウイルス / デング熱 / デング出血熱 / マーモセット / 個体 / 動物モデル

Research Abstract

Dengue virus infection is one of the most important mosquito-borne virus infectious diseases in the world. We developed an animal model to analyze the pathogenesis of dengue fever, using common marmosets. Marmosets demonstrated high levels of viremia after dengue virus infection. Marmosets also demonstrated antibody responses, and hematological and biochemical changes similar to those detected in dengue fever patients. Immunological methods to detect cytokines and cellular markers were developed, in order to precisely analyze T cell immune responses in marmosets.

Research Products

• [Journal Article] Immune-Related Gene Expression Profile in Laboratory Common Marmosets Assessed by an Accurate Quantitative Real-Time PCR Using Selected Reference Genes. (2013)
  • Author(s): Fujii Y
  • Journal Title: Pros ONE Volume: 8 Issue: 2 Pages: e56296-e56296
  • DOI: 10.1371/journal.pone.0056296
  • Peer Reviewed
• [Journal Article] Presence of viral genome in urine and development of hematuria and pathological changes in kidneys in common marmoset (Callithrix jacchus) after inoculation with dengue virus. (2013)
  • Author(s): Moi, M.L., Omatsu, T., Hirayama, T., Nakamura, S., Katakai, Y., Yoshida, T., Saito, A., Tajima, S., Ito, M., Takasaki, T., Akari, H. and Kurane, I
  • Journal Title: Pathogens Volume: 2 Pages: 357-393
• [Journal Article] Changes in hematological and serum biochemical parameters in common marmosets (Callithrix jacchus) after inoculation with dengue virus. (2012)
  • Author(s): Omatsu, T., Moi, M.L., Takasaki, T., Nakamura, S., Katakai, Y., Tajima, S., Ito, M., Yoshida, T., Saito, A., Akari, H. and Kurane, I
  • Journal Title: Journal of Medical Primatology Volume: 41(5) Issue: 5 Pages: 289-296
  • DOI: 10.1111/j.1600-0684.2012.00552.x
• [Journal Article] A new method for quantitative analysis of the T cell receptor V region repertoires in healthy common marmosets by microplate hybridization assay. (2012)
  • Author(s): Kitaura K
  • Journal Title: J Immunol Methods Volume: 364 Issue: 1-2 Pages: 81-91
  • DOI: 10.1016/j.jim.2012.07.012
  • Peer Reviewed
• [Journal Article] Changes in hematological and serum biochemical parameters in common marmosets (Callithrix jacchus) after inoculation with dengue virus. (2012)
  • Author(s): Omatsu, T., Moi, M.L., Takasaki, T., Nakamura, S., Katakai, Y., Tajim1’10-1’2a, S., Ito, M., Yoshida, T., Saito, A., Akari, H. and Kurane, I.
  • Journal Title: Journal of Medical Primatology. Volume: 41(5) Pages: 289-296
  • Peer Reviewed
• [Journal Article] A new method for quantitative analysis of the T cell receptor V region repertoires in healthy common marmosets by microplate hybridization assay. (2012)
  • Author(s): Kitaura, K., Fujii, Y., Matsutani, T., Shirai, K., Suzuki, S., Takasaki, T., Shimada, S., Kametani, Y., Shiina, T., Takabayashi, S., Katoh, H., Ogasawara, K., Kurane, I. and Suzuki, R.
  • Journal Title: Journal of Imunological Methods. Volume: 384(1-2) Pages: 81-91
  • Peer Reviewed
• [Journal Article] Common marmoset (Callithrix jacchus) as a primate model of dengue virus infection: development of high levels of viremia and demonstration of protective immunity. (2011)
  • Author(s): Omatsu, T., Moi, M.L., Hirayama., T., Takasaki, T., Nakamura, S., Tajima, S., Ito, M., Yoshida, T., Saito, A., Katakai, Y., Akari, H. and Kurane, I
  • Journal Title: Journal of General Virology Volume: 92(Pt10) Issue: 10 Pages: 2272-2280
  • DOI: 10.1099/vir.0.031229-0
  • Peer Reviewed
• [Journal Article] Increased positive selection pressure within the CDR regions of the T cell receptor β gene in New World monkeys (2011)
  • Author(s): Matsutani T, Fujii Y, Kitaura K, Suzuki S, Tsuruta Y, Itoh T, Nishimoto N, Takasaki T, Kurane I, Suzuki R
  • Journal Title: Am J Primatol Volume: 73 Issue: 10 Pages: 1082-1092
  • DOI: 10.1002/ajp.20976
  • Peer Reviewed
• [Journal Article] Common marmoset (Callithrix jacchus) as a primate model of dengue virus infection : development of high levels of viraemia and demonstration of protective immunity (2011)
  • Author(s): Omatsu T, Moi ML, Hirayama T, Takasaki T, Nakamura S, Tajima S, Ito M, Yoshida T, Saito A, Katakai Y, Akari H, Kurane I
  • Journal Title: J Gen Virol Volume: 92(Pt10) Pages: 2272-80
  • Peer Reviewed
• [Journal Article] Shortening of complementarity determining region 3 of the T cell receptor a chain during thymocyte development. (2011)
  • Author(s): Matsutani T, Ogata M, Fujii Y, Kitaura K, Nishimoto N, Suzuki R, Itoh T.
  • Journal Title: Molecular Immunology Volume: 48(4) Pages: 623-629
  • Peer Reviewed
• [Journal Article] Comprehensive analysis and characterization of the TCR alpha chain sequences in the common marmoset (2010)
  • Author(s): Fujii, K., Matsutani, T., Kitaura, K., Suzuki, S., Itoh, T., Takasaki, T., Suzuki, R. and Kurane, I
  • Journal Title: Immunogenetics Volume: 41(5) Issue: 6 Pages: 383-385
  • DOI: 10.1007/s00251-010-0445-0
• [Journal Article] Comprehensive analysis and characterization of the TCR alpha chain sequences in the common marmoset. (2010)
  • Author(s): Fujii Y, Matsutani T, Kitaura K, Suzuki S, Itoh T, Takasaki T, Suzuki R, Kurane I.
  • Journal Title: Immunogenetics. Volume: 62(6) Pages: 383-395
  • Peer Reviewed
• [Presentation] コモンマーモセットにおけるリアルタイムPCRを用いた免疫関連遺伝子発現解析 (2013)
  • Author(s): 北浦一孝、藤井克樹、松谷隆治、白井顕治、鈴木さつき、高崎智彦、亀谷美恵、倉根一郎、鈴木隆二
  • Organizer: 第60回日本実験動物学会総会
  • Place of Presentation: つくば
• [Presentation] コモンマーモセットにおけるTCRレパトア解析法の開発 (2012)
  • Author(s): 北浦一孝、藤井克樹、松谷隆治、白井顕治、鈴木さつき、高崎智彦、倉根一郎、鈴木隆二
  • Organizer: 第59回日本実験動物学会総会
  • Place of Presentation: 別府
• [Presentation] 新世界ザルにおけるT細胞受容体β鎖遺伝子のCDR3領域における正の選択 (2011)
  • Author(s): 北浦一孝、松谷隆治、藤井克樹、白井顕治、鈴木さつき、高崎智彦、小笠原康悦、西本憲弘、倉根一郎、鈴木隆二
  • Organizer: 第40回日本免疫学会学術集会
  • Place of Presentation: 東京
• [Presentation] Role of antibodies in dengue protective immunity and infection during secondary infection of marmosets.
  • Author(s): 倉根一郎、モイ メンリン、大松勉、高崎智彦、中村紳一朗、綱康至、片貝祐子、須崎百合子、明里宏文
  • Organizer: 第60回日本ウイルス学会学術集会
  • Place of Presentation: 大阪国際会議場