Analysis of measles pathogenesis using the mouse model expressing measles virus receptor SLAM and recombinant viruses

• Project/Area Number: 17209016
• Research Category: Grant-in-Aid for Scientific Research (A)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Virology
• Research Institution: Kyushu University
• Principal Investigator: YANAGI Yusuke Kyushu University, 大学院・医学研究院, 教授 (40182365)
• Co-Investigator(Kenkyū-buntansha): TAKEDA Makoto 九州大学, 大学院・医学研究院, 准教授 (40311401) ; 大野 真治 九州大学, 大学院・医学研究院, 講師 (50419529)
• Co-Investigator(Renkei-kenkyūsha): OHNO Shinji 九州大学, 大学院・医学研究院, 講師 (50419529)
• Project Period (FY): 2005 – 2008
• Project Status: Completed (Fiscal Year 2008)
• Budget Amount: ¥50,700,000 (Direct Cost: ¥39,000,000、Indirect Cost: ¥11,700,000); Fiscal Year 2008: ¥13,520,000 (Direct Cost: ¥10,400,000、Indirect Cost: ¥3,120,000); Fiscal Year 2007: ¥13,520,000 (Direct Cost: ¥10,400,000、Indirect Cost: ¥3,120,000); Fiscal Year 2006: ¥13,520,000 (Direct Cost: ¥10,400,000、Indirect Cost: ¥3,120,000); Fiscal Year 2005: ¥10,140,000 (Direct Cost: ¥7,800,000、Indirect Cost: ¥2,340,000)
• Keywords: 麻疹ウイルス / 受容体 / SLAM / 動物モデル / 組換えウイルス / ウイルス受容体 / CD150

Research Abstract

麻疹(ましん、はしか)は発熱、発疹、免疫抑制、時に脳炎を起こす小児の重要なウイルス感染症である。麻疹ウイルスが病気を起こすメカニズムを明らかにするために、ウイルスの受容体であるヒトSLAM分子を発現する遺伝子改変マウスを作製した。このマウスは、ヒトで見られる麻疹ウイルスの感染、免疫抑制作用、毒力を非常によく再現し、優れた動物モデルとなることが示された。様々な組換えウイルスを感染させることにより、病態の解析が容易となった。

Research Products

• [Journal Article] Measles virus receptors (2009)
  • Author(s): Yanagi Y, Takeda M, Ohno S, Hashiguchi T.
  • Journal Title: Curr Top Microbiol Immunol 329 Pages: 13-30
• [Journal Article] Measles virus receptors (2009)
  • Author(s): Yanagi Y, et al.
  • Journal Title: Curr Top Microbiol Immunol 329 Pages: 13-30
  • Peer Reviewed
• [Journal Article] Measles viruses possessing the polymerase protein genes of the Edmonston vaccine strain exhibit attenuated gene expression and growth in cultured cells and SLAM knock-in mice (2008)
  • Author(s): Takeda M, Ohno S, Tahara M, Takeuchi H, Shirogane Y, Ohmura H, Nakamura T, Yanagi Y.
  • Journal Title: J Virol. 82 Pages: 11979-11984
• [Journal Article] Measles virus infects both polarized epithelial and immune cells using distinctive receptor-binding sites on its hemagglutinin. (2008)
  • Author(s): Tahara M, et al.
  • Journal Title: J Virol J Virol Pages: 4630-4637
  • Peer Reviewed
• [Journal Article] Efficient multiplication of human metapneumovirus in Vero cells expressing the transmembrane serine protease TMPRSS2. (2008)
  • Author(s): Shirogane Y, et al.
  • Journal Title: J Virol 82 Pages: 8942-8246
  • Peer Reviewed
• [Journal Article] Measles virus circumvents the host interferon response by different actions of the C and V proteins. (2008)
  • Author(s): Nakatsu Y, et al.
  • Journal Title: J Virol 82 Pages: 8296-8306
  • Peer Reviewed
• [Journal Article] Measles viruses possessing the polymerase protein genes of the Edmonston vaccine strain exhibit attenuated gene expression and growth in cultured cells and SLAM knock-in mice. (2008)
  • Author(s): Takeda M, et al.
  • Journal Title: J Virol 82 Pages: 11979-11984
  • Peer Reviewed
• [Journal Article] Measles virus infects both polarized epithelial and immune cells using distinctive receptor-binding sites on its hemagglutinin. (2008)
  • Author(s): Tahara M, et. al.
  • Journal Title: J Virol 82(in press)
  • Peer Reviewed
• [Journal Article] Dynamic interaction of the measles virus hemagglutinin with its receptor SLAM. (2008)
  • Author(s): Navaratnarajah CK, et. al.
  • Journal Title: JBiol Chem (in press)
  • Peer Reviewed
• [Journal Article] Homogeneous sugar modification improves crystallization of measles virus hemagglutinin. (2008)
  • Author(s): Hashiguchi T, et. al.
  • Journal Title: J Virol Methods 149 Pages: 171-174
  • Peer Reviewed
• [Journal Article] Predominant Infection of CD150(+)Lymphocytes and Dendritic Cells during Measles Virus Infection of Macaques (2007)
  • Author(s): de Swart RL, Ludlow M, de Witte L, Yanagi Y, van Amerongen G, McQuaid S, Yuksel S, Geijtenbeek TB, Duprex WP, Osterhaus AD
  • Journal Title: PLoS Pathog 3 : e178
• [Journal Article] Measles virus infection of SLAM(CD150)knockin mice reproduces tropism and immunosuppression in human infection (2007)
  • Author(s): Ohno S, Ono N, Seki F, Takeda M, Kura S, Tsuzuki T, Yanagi Y.
  • Journal Title: J Virol. 81 Pages: 1650-1659
• [Journal Article] SAP Regulation of Follicular Helper CD4 T Cell Development and Humoral Immunity Is Independent of SLAM and Fyn Kinase (2007)
  • Author(s): McCausland MM, Yusuf I, Tran H, Ono N, Yanagi Y, Crotty S.
  • Journal Title: J Immunol 178 Pages: 817-828
• [Journal Article] Altered interaction of the matrix protein with the cytoplasmic tail of hemagglutinin modulates measles virus growth by affecting virus assembly and cell-cell fusion. (2007)
  • Author(s): Tahara M, et. al.
  • Journal Title: J Virol 81 Pages: 6827-6836
  • Peer Reviewed
• [Journal Article] A human lung carcinoma cell line supports efficient measles virus growth and syncytium formation via a SLAM-and CD46-independent mechanism. (2007)
  • Author(s): Takeda M, et. al.
  • Journal Title: J Virol 81 Pages: 12091-12096
  • Peer Reviewed
• [Journal Article] Crystal struture of measles virus hemagglutinin provides insight into effective vaccines. (2007)
  • Author(s): Hashiguchi T, et. al.
  • Journal Title: Proc Natl Acad Sci U S A 104 Pages: 19535-19540
  • Peer Reviewed
• [Journal Article] Predominant Infection of CD150(+)Lymphocytes and Dendritic Cells during Measles Virus Infection of Macaques. (2007)
  • Author(s): de Swart RL, et. al.
  • Journal Title: PLoS Pathog 3
  • Peer Reviewed
• [Journal Article] Measles virus infection of SLAM (CD150) knockin mice reproduces tropism and immunosuppression in human infection (2007)
  • Author(s): Ohno S et al.
  • Journal Title: J Virol 81(4) Pages: 1650-1659
• [Journal Article] SAP Regulation of Follicular Helper CD4 T Cell Development and Humoral Immunity Is Independent of SLAM and Fyn Kinase (2007)
  • Author(s): McCausland MM et al.
  • Journal Title: J Immunol 78(2) Pages: 817-828
• [Journal Article] Multiple Amino Acid Substitutions in Hemagglutinin Are Necessary for Wild-Type Measles Virus To Acquire Ability To Use Receptor CD46 Efficiently (2007)
  • Author(s): Tahara M et al.
  • Journal Title: J Virol 81(6) Pages: 2564-2572
• [Journal Article] Measles virus : cellular receptors, tropism and pathogenesis (2006)
  • Author(s): Yanagi Y, Takeda M, Ohno S.
  • Journal Title: J Gen Virol. 87 Pages: 2767-2779
• [Journal Article] Recombinant wild-type measles virus containing a single N481Y substitution in its haemagglutinin cannot use receptor CD46 as efficiently as that having the haemagglutinin of the Edmonston laboratory strain (2006)
  • Author(s): Seki F, Takeda M, Minagawa H, Yanagi Y.
  • Journal Title: J Gen Virol. 87 Pages: 1643-1648
• [Journal Article] Rescue system for measles virus from cloned cDNA driven by vaccinia virus Lister vaccine strain (2006)
  • Author(s): Nakatsu Y, Takeda M, Kidokoro M, Kohara M, Yanagi Y.
  • Journal Title: J Virol Methods 137 Pages: 152-155
• [Journal Article] Generation of measles virus with a segmented RNA genome (2006)
  • Author(s): Takeda M, Nakatsu Y, Ohno S, Seki F, Tahara M, Hashiguchi T, Yanagi Y.
  • Journal Title: J Virol. 80 Pages: 4242-4248
• [Journal Article] Generation of measles virus with a segmented RNA genome (2006)
  • Author(s): Takeda M et al.
  • Journal Title: J Virol 80(9) Pages: 4242-4248
• [Journal Article] Recombinant wild-type measles virus containing a single N481Y substitution in its haemagglutinin cannot use receptor CD46 as efficiently as that having the haemagglutinin of the Edmonston laboratory strain (2006)
  • Author(s): Seki F et al.
  • Journal Title: J Gen Virol 87(6) Pages: 1643-1648
• [Journal Article] Rescue system for measles virus from cloned cDNA driven by vaccinia virus Lister vaccine strain (2006)
  • Author(s): Nakatsu Y et al.
  • Journal Title: J Virol Methods 137(1) Pages: 152-155
• [Journal Article] Measles virus : cellular receptors, tropism and pathogenesis (2006)
  • Author(s): Yanagi Y et al.
  • Journal Title: J Gen Virol 87(10) Pages: 2767-2779
• [Journal Article] Translational inhibition and increased interferon induction in cells infected with C protein-deficient measles virus (2006)
  • Author(s): Nakatsu Y et al.
  • Journal Title: J Virol 80(23) Pages: 11861-11867
• [Journal Article] Measles virus receptors and tropism (2006)
  • Author(s): Yanagi Y et al.
  • Journal Title: Japanese Journal of Infectious Diseases 59 Pages: 1-5
  • NAID: 40007325329
• [Journal Article] Generation of measles virus with a segmented RNA genome (2006)
  • Author(s): Takeda M et al.
  • Journal Title: Journal of Virology 80(in press)
• [Journal Article] The recombinant wild-type measles virus containing a single N481Y substitution in its haemagglutinin cannot use receptor CD46 as efficiently as that having the haemagglutinin of the Edmonston Laboratory strain (2006)
  • Author(s): Seki F et al.
  • Journal Title: Journao of General Virology 87(in press)
• [Journal Article] Contributions of matrix and large protein genes of the measles virus Edmonston strain to growth in cultured cells as revealed by recombinant viruses (2005)
  • Author(s): Tahara M, Takeda M, Yanagi Y.
  • Journal Title: J Virol. 79 Pages: 15218-15225
• [Journal Article] Long untranslated regions of the measles virus M and F genes control virus replication and cytopathogenicity (2005)
  • Author(s): Takeda M, Ohno S, Seki F, Nakatsu Y, Tahara M, Yanagi Y.
  • Journal Title: J Virol. 79 Pages: 14346-14354
• [Journal Article] Efficient rescue of measles virus from cloned cDNA using SLAM-expressing Chinese hamster ovary cells (2005)
  • Author(s): Takeda M, Ohno S, Seki F, Hashimoto K, Miyajima N, Takeuchi K, Yanagi Y.
  • Journal Title: Virus Res. 108 Pages: 161-165
• [Journal Article] Efficient rescue of measles virus from cloned cDNA using SLAM-expressing Chinese hamster ovary cells (2005)
  • Author(s): Takeda M et al.
  • Journal Title: Virus Research 108 Pages: 161-165
• [Journal Article] Long untranslated regions of the measles virus M and F genes control virus replication and cytopathogenicity (2005)
  • Author(s): Takeda M et al.
  • Journal Title: Journal of Virology 79 Pages: 14346-14354
• [Journal Article] Contributions of matrix and large protein genes of the measles virus Edmonston strain to growth in cultured cells as revealed by recombinant viruses (2005)
  • Author(s): Tahara M et al.
  • Journal Title: Journal of Virology 79 Pages: 15218-15225
• [Presentation] 麻疹ウイルスHタンパク質による受容体認識の構造基盤 (2008)
  • Author(s): 橋口隆生, 竹田誠, 田原舞乃, 池亀聡, 大野真治, 柳雄介
  • Organizer: 第56回 日本ウイルス学会
  • Place of Presentation: 岡山
  • Year and Date: 2008-10-28
• [Presentation] ポリメラーゼ遺伝子は麻疹ウイルスEdmonston株の弱毒化を担っている (2008)
  • Author(s): 竹田誠、大野真治、田原舞乃、白銀勇太、柳雄介
  • Organizer: 第56回日本ウイルス学会
  • Place of Presentation: 岡山
  • Year and Date: 2008-10-26
• [Presentation] 麻疹ウイルスMタンパク質機能発現機構の解析 (2008)
  • Author(s): 岩崎正治, 竹田誠, 中津祐一郎, 白銀勇太, 中村崇規, 柳雄介
  • Organizer: 第56回 日本ウイルス学会
  • Place of Presentation: 岡山
  • Year and Date: 2008-10-26
• [Presentation] 麻疹ウイルスの極性細胞侵入および出芽機構 (2008)
  • Author(s): 竹田誠, 橋口隆生, 田原舞乃, 岩崎正治, 池亀聡, 柳雄介
  • Organizer: 第56回 日本ウイルス学会
  • Place of Presentation: 岡山
  • Year and Date: 2008-10-26
• [Presentation] 宿主細胞の麻疹ウイルス感染認識機構と麻疹ウイルスVタンパク質の役割 (2008)
  • Author(s): 池亀聡, 竹田誠, 大野真治, 中津祐一郎, 柳雄介
  • Organizer: 第56回 日本ウイルス学会
  • Place of Presentation: 岡山
  • Year and Date: 2008-10-26
• [Presentation] 麻疹ウイルスマトリックスタンパク質とヌクレオカプシドタンパク質問相互作用の解析 (2008)
  • Author(s): 岩崎正治, 竹田誠, 中津祐一郎, 白銀勇太, 中村崇規, 柳雄介
  • Organizer: 第45回 日本ウイルス学会九州支部総会
  • Place of Presentation: 熊本
  • Year and Date: 2008-10-03
• [Presentation] 麻疹ウイルスの極性上皮細胞からの出芽機構 (2008)
  • Author(s): 竹田誠, 岩崎正治, 池亀聡, 田原舞乃, 柳雄介
  • Organizer: 第45回 日本ウイルス学会九州支部総会
  • Place of Presentation: 熊本
  • Year and Date: 2008-10-03
• [Presentation] X線結晶構造解析による麻疹ウイルスHタンパク質のレセプター認識の構造基盤 (2007)
  • Author(s): 橋口 隆生、竹田 誠、柳 雄介
  • Organizer: 第55回日本ウイルス学会
  • Place of Presentation: 札幌
  • Year and Date: 2007-10-22
• [Presentation] 病原性麻疹ウイルスのV,C蛋白は独立して感染細胞のアポトーシスを抑制する (2007)
  • Author(s): 大野 真治、柳 雄介
  • Organizer: 第55回日本ウイルス学会
  • Place of Presentation: 札幌
  • Year and Date: 2007-10-22
• [Presentation] 麻疹ウイルスV蛋白質によるJAK-STAT経路の阻害メカニズムの解析 (2007)
  • Author(s): 百田 匡寿、大野 真治、柳 雄介
  • Organizer: 第55回日本ウイルス学会
  • Place of Presentation: 札幌
  • Year and Date: 2007-10-22
• [Presentation] 肺癌細胞株を用いた麻疹ウイレスの新たな感染機構の解析 (2007)
  • Author(s): 竹田 誠、田原 舞乃、橋口 隆生、佐藤 威、植木 翔子、大野 真治、柳 雄介
  • Organizer: 第55回日本ウイルス学会
  • Place of Presentation: 札幌
  • Year and Date: 2007-10-22
• [Presentation] 麻疹ウイルス感染におけるレセプターSLAM上の糖鎖の意義 (2007)
  • Author(s): 橋口 隆生、久保田 万理恵、竹田 誠、大野 真治、柳 雄介
  • Organizer: 第55回日本ウイルス学会
  • Place of Presentation: 札幌
  • Year and Date: 2007-10-22
• [Presentation] ヒト SLAM ノックインマウスの麻疹ウイルス感染の解析 (2006)
  • Author(s): 大野真治、小野伸之、関文緒、竹田誠、柳雄介
  • Organizer: 第54回日本ウイルス学会
  • Place of Presentation: 名古屋
  • Year and Date: 2006-11-21
• [Presentation] Analysis of measles virus infection using human SLAM knock-in mice (2006)
  • Author(s): Ohno S, Ono N, Seki F, Takeda M, Yanagi Y.
  • Organizer: The 6th Awaji International Forum on Infection and Immunity
  • Place of Presentation: Awaji Island, Hyogo
  • Year and Date: 2006-09-06
• [Remarks]
  • URL: http://www.med.kyushu-u.ac.jp/virus/index.html
• [Remarks]
  • URL: http://www.med.kyushu-u.ac.jp/virus/index.html
• [Remarks]
  • URL: http://www.med.kyushu-u.ac.jp/virus/index.html