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A study of the participation of viral anti-apoptotic factor in the pathogenesis of developmental brain disorders induced by viral infection

Research Project

Project/Area Number 20590396
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Experimental pathology
Research InstitutionHamamatsu University School of Medicine

Principal Investigator

KOSUGI Isao  Hamamatsu University School of Medicine, 医学部, 准教授 (10252173)

Co-Investigator(Renkei-kenkyūsha) KAWASAKI Hideya  浜松医科大学, 医学部, 助教 (90397381)
ARAI Yoshifumi  浜松医科大学, 医学部, 助教 (30381784)
Project Period (FY) 2008 – 2010
Project Status Completed (Fiscal Year 2010)
Budget Amount *help
¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000)
Fiscal Year 2010: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2009: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2008: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
Keywords発生病理 / ウイルス感染症 / サイトメガロウイルス / 神経細胞 / 脳発達障害 / 神経細胞死 / ネクローシス / 興奮毒性細胞死 / アポトーシス
Research Abstract

Virus-derived anti-apoptotic protein not only blocks cell death, but also establishes persistent infection, resulting in functional disturbances and malignant transformation of host cells. Cytomegalovirus (CMV) persistently infects developing cerebral neurons, and is the leading viral cause of developmental brain disorders in humans. In this study, we have investigated the impact of M45 protein, a representative of CMV-derived anti-apoptotic proteins, on the development of cerebral neurons. Wild type CMV inhibited the arborization of dendrites in developing neurons, however, M45-deleted CMV did not. This result indicates that M45 protein not only blocks cell death, but also disturbs neuronal development.

Report

(4 results)
  • 2010 Annual Research Report   Final Research Report ( PDF )
  • 2009 Annual Research Report
  • 2008 Annual Research Report
  • Research Products

    (53 results)

All 2011 2010 2009 2008 Other

All Journal Article (20 results) (of which Peer Reviewed: 16 results) Presentation (29 results) Remarks (4 results)

  • [Journal Article] A case of Epstein-Barr virus associated post-transplant lymphoproliferative disorder with central nervous system involvement.2011

    • Author(s)
      Suzuki, M., Kosugi I., Terada, T., et al.
    • Journal Title

      Neuropathology 31

    • Related Report
      2010 Final Research Report
    • Peer Reviewed
  • [Journal Article] Mouse Embryonic Stem Cells Inhibit Marine Cytomegalovirus Infection through a Multi-Step Process.2011

    • Author(s)
      Kawasaki H, Kosugi I, Arai Y, Iwashita T, Tsutsui Y.
    • Journal Title

      PLoS One 6

    • Related Report
      2010 Final Research Report
    • Peer Reviewed
  • [Journal Article] Mouse Embryonic Stem Cells Inhibit Murine Cytomegalovirus Infection through a Multi-Step Process2011

    • Author(s)
      Kawasaki H, Kosugi I, Arai Y, Iwashita T, Tsutsui Y.
    • Journal Title

      PLoS One

      Volume: 6

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] A case of Epstein-Barr virus associated post-transplant lymphoproliferative disorder with central nervous system involvement2011

    • Author(s)
      Suzuki, M., Kosugi, I., Terada, T., et al.
    • Journal Title

      Neuropathology

      Volume: 31

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] In vivo imaging assay for the convenient evaluation of antiviral compounds against cytomegalovirus in mice.2010

    • Author(s)
      Yamada, S., Kosugi I., Katano, H, Fukui, Y., Kawasaki, H., Arai, Y., Kcrane, I., Inoue, N.
    • Journal Title

      Antiviral Res 88

      Pages: 45-52

    • Related Report
      2010 Final Research Report
    • Peer Reviewed
  • [Journal Article] Aggressive progression of breast cancer with microscopic pulmonary emboli possessing a stem cell-like phenotype independent of its origin.2010

    • Author(s)
      Kawasaki, H., Ogura, H., Arai, Y., Baba, S., Kosugi I., et al.
    • Journal Title

      Pathol Int 60

      Pages: 228-234

    • NAID

      10029331202

    • Related Report
      2010 Final Research Report
    • Peer Reviewed
  • [Journal Article] 特集:ヘルペスウイルスHHV-5(CMV)2010

    • Author(s)
      小杉伊三夫
    • Journal Title

      ウイルス 66

      Pages: 209-220

    • Related Report
      2010 Final Research Report
  • [Journal Article] In vivo imaging assay for the convenient evaluation of antiviral compounds against cytomegalovirus in mice2010

    • Author(s)
      Yamada, S., Kosugi, I., Katano, H., Fukui, Y., Kawasaki, H., Arai, Y., Kurane, I., Inoue, N
    • Journal Title

      Antiviral Res

      Volume: 88 Pages: 45-52

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Aggressive progression of breast cancer with microscopic pulmonary emboli possessing a stem cell-like phenotype independent of its origin2010

    • Author(s)
      Kawasaki, H., Ogura, H., Arai, Y., Baba, S., Kosugi, I., et al.
    • Journal Title

      Pathol Int

      Volume: 60 Pages: 228-234

    • NAID

      10029331202

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] 特集:ヘルペスウイルスHHV-5(CMV)2010

    • Author(s)
      小杉伊三夫
    • Journal Title

      ウイルス

      Volume: 66 Pages: 209-220

    • Related Report
      2010 Annual Research Report
  • [Journal Article] Aggressive progression of breast cancer with microscopic pulmonary emboli possessing a stem cell-like phenotype independent of its origin2010

    • Author(s)
      Kawasaki H, Ogura H, Arai Y, Baba S, Kosugi I, Tsutsui Y, Iwashita T.
    • Journal Title

      Pathology International 60

      Pages: 228-34

    • NAID

      10029331202

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Adenovirus EIA inhibits SCF(Fbw7) ubiquitin ligase.2009

    • Author(s)
      Isobe T, Hattori T, Kitagawa K, Uchida C, Kotake Y, Kosugi I, Oda T, Kitagawa M.
    • Journal Title

      Journal of Biologocal Chemistry 284

      Pages: 27766-27779

    • Related Report
      2010 Final Research Report
    • Peer Reviewed
  • [Journal Article] 幹細胞とウイルス感染症2009

    • Author(s)
      小杉伊三夫、梁明秀
    • Journal Title

      医学のあゆみ 229

      Pages: 720-725

    • Related Report
      2010 Final Research Report
  • [Journal Article] Adenovirus E1A inhibits SCF (Fbw7) ubiquitin ligase2009

    • Author(s)
      Isobe T, Hattori T, Kitagawa K, Uchida C, Kotake Y, Kosugi I, Oda T, Kitagawa M.
    • Journal Title

      Journal of Biologocal Chemistry 284

      Pages: 27766-79

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Journal Article] 幹細胞とウイルス感染症2009

    • Author(s)
      小杉伊三夫, 梁明秀
    • Journal Title

      医学のあゆみ 229

      Pages: 720-25

    • Related Report
      2009 Annual Research Report
  • [Journal Article] Induction of cytomegalovirus-infected labyrinthitis in newborn mice by lipopolysaccharide, a model for hearing loss in congenital CMV infection.2008

    • Author(s)
      Li L, Kosugi I, Ilan GP, Kawasaki H, Arai Y, Takeshita T, Tsutsui Y
    • Journal Title

      Lab Invest. 88(7)

      Pages: 722-730

    • Related Report
      2010 Final Research Report
    • Peer Reviewed
  • [Journal Article] Establishment of a Cell-Based Assay for Screening of Compounds Inhibiting Very Early Events in the Cytomegalovirus Replication Cycle and Characterization of a Compound Identified Using the Assay Antimicrob2008

    • Author(s)
      Fukui Y, Shindoh K, Yamamoto Y, Koyano S, Kosugi I, Yamaguchi T, Kurane I, Inoue N
    • Journal Title

      Agents Chemother Vol.52, No.7

      Pages: 2420-2427

    • Related Report
      2010 Final Research Report
    • Peer Reviewed
  • [Journal Article] Roles of neural stem progenitor cells in cytomegalovirus infection of the brain in mouse models.2008

    • Author(s)
      Tsutsui Y, Kosugi I, Kawasaki H, Arai Y, Han GP, Li L, Kaneta M
    • Journal Title

      Pathol Iot 58(5)

      Pages: 257-267

    • NAID

      10027376380

    • Related Report
      2010 Final Research Report
    • Peer Reviewed
  • [Journal Article] Induction of cytomegalovirus-infected labyrinthitis in newborn mice by lipopolysaccharide : a model for hearing loss in congenital CMV infection.2008

    • Author(s)
      Li L, Kosugi I, Han GP, Kawasaki H, Arai Y, Takeshita T, Tsutsui Y.
    • Journal Title

      Laboratory Investigation 88

      Pages: 722-30

    • Related Report
      2008 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Roles of neural stem progenitor cells in cytomegalovirus infection of the brain in mouse models.2008

    • Author(s)
      Tsutsui Y, Kosugi I, Kawasaki H, Arai Y, Han GP, Li L, Kaneta M.
    • Journal Title

      Pathology International 58

      Pages: 257-67

    • NAID

      10027376380

    • Related Report
      2008 Annual Research Report
    • Peer Reviewed
  • [Presentation] 発育期大脳神経細胞におけるマウスサイトメガロウイルス感染と脳発達障害2010

    • Author(s)
      小杉伊三夫
    • Organizer
      第58回日本ウイルス研究会
    • Place of Presentation
      徳島
    • Year and Date
      2010-11-05
    • Related Report
      2010 Final Research Report
  • [Presentation] 発育期大脳神経細胞におけるサイトメガロウイルス感染と脳発達障害2010

    • Author(s)
      小杉伊三夫, 河崎秀陽, 新井義文, 岩下寿秀, 筒井祥博
    • Organizer
      第58回日本ウイルス学会学術集会
    • Place of Presentation
      徳島
    • Year and Date
      2010-11-05
    • Related Report
      2010 Annual Research Report
  • [Presentation] Screening and characterization of chemical compounds that inhibit early phase of CMV and VZV infections2010

    • Author(s)
      山田壮一, 小杉伊三夫, 片野晴隆, 倉根一郎, 井上直樹
    • Organizer
      第14回国際ヘルペスウイルス感染症学会
    • Place of Presentation
      神戸
    • Year and Date
      2010-10-06
    • Related Report
      2009 Annual Research Report
  • [Presentation] In vivo imaging assay for the convenient evaluation of antiviral compounds against cytomegalovirus in mice2010

    • Author(s)
      Yamada, S., Kosugi, L, Katano, H., Fukui, Y., Kawasaki, H., Arai, Y, Kurane, I., N.Inoue
    • Organizer
      Congenital Cytomegalovirus Conference
    • Place of Presentation
      Paris, France
    • Year and Date
      2010-09-15
    • Related Report
      2010 Annual Research Report
  • [Presentation] ES細胞におけるサイトメガロウイルス感染感受性の多段階的制御とその機序2010

    • Author(s)
      河崎秀陽、小杉伊三夫、新井義文、岩下寿秀、筒井祥博
    • Organizer
      第50回日本先天異常学会学術集会
    • Place of Presentation
      淡路
    • Year and Date
      2010-07-20
    • Related Report
      2010 Annual Research Report
  • [Presentation] 発育期大脳神経細胞におけるマウスサイトメガロウイルス感染と脳発達障害2010

    • Author(s)
      小杉伊三夫
    • Organizer
      第25回ヘルペスウイルス研究会
    • Place of Presentation
      浜松
    • Year and Date
      2010-05-27
    • Related Report
      2010 Final Research Report
  • [Presentation] 発育期大脳神経細胞におけるサイトメガロウイルス感染と脳発達障害2010

    • Author(s)
      小杉伊三夫, 河崎秀陽, 新井義文, 岩下寿秀, 筒井祥博
    • Organizer
      第25回ヘルペスウイルス研究会
    • Place of Presentation
      浜松
    • Year and Date
      2010-05-27
    • Related Report
      2010 Annual Research Report
  • [Presentation] GFP発現組換えマウスサイトメガロウイルスを用いたin vivo imagingによる抗ヘルペスウイルス薬in vivo評価系の確立2010

    • Author(s)
      山田壮一、小杉伊三夫、片野晴隆、福井良子、河崎秀陽、新井義文、福地早紀、橋本楓、倉根一郎、井上直樹
    • Organizer
      第25回ヘルペスウイルス研究会
    • Place of Presentation
      浜松
    • Year and Date
      2010-05-27
    • Related Report
      2010 Annual Research Report
  • [Presentation] 発育期大脳神経細胞におけるサイトメガロウイルス持続感染と脳発達障害:感染神経細胞における樹状突起の解析2010

    • Author(s)
      小杉伊三夫
    • Organizer
      第99回日本病理学会総会
    • Place of Presentation
      東京
    • Year and Date
      2010-04-28
    • Related Report
      2010 Final Research Report
  • [Presentation] 発育脳神経細胞におけるサイトメガロウイルス感染と脳発達障害:感染神経細胞における樹状突起の解析2010

    • Author(s)
      小杉伊三夫, 河崎秀陽, 新井義文, 岩下寿秀, 筒井祥博
    • Organizer
      第99回日本病理学会総会
    • Place of Presentation
      東京
    • Year and Date
      2010-04-28
    • Related Report
      2010 Annual Research Report
  • [Presentation] ES細胞におけるサイトメガロウイルス感染感受性の多段階的制御とその機序2010

    • Author(s)
      河崎秀陽, 小杉伊三夫, 新井義文, 岩下寿秀、筒井祥博
    • Organizer
      第99回日本病理学会
    • Place of Presentation
      東京
    • Year and Date
      2010-04-28
    • Related Report
      2010 Annual Research Report
  • [Presentation] Bacterial artificial chromosomeを用いた組織標本中のウイルスゲノム同定法2010

    • Author(s)
      新井義文, 小杉伊三夫, 河崎秀陽, 岩下寿秀, 筒井祥博
    • Organizer
      第99回病理学会総会
    • Place of Presentation
      東京
    • Year and Date
      2010-04-28
    • Related Report
      2010 Annual Research Report
  • [Presentation] In vivo imaging assay for the convenient evaluation of antiviral compounds against cytomegalovirus in mice2010

    • Author(s)
      Yamada, S., Kosugi I., Katano, H., Fukui, Y. , Kawasaki, H., Arai, Y., Kurane, I., N.Inoue.
    • Organizer
      2010 Congenital Cytomegalovirus Conference
    • Place of Presentation
      France
    • Related Report
      2010 Final Research Report
  • [Presentation] 発育期神経細胞におけるサイトメガロウイルス感染と脳発達障害 : 感染神経細胞に特徴的なNF-κB核内局在の解析2009

    • Author(s)
      小杉伊三夫, 河崎秀陽, 新井義文, 筒井祥博
    • Organizer
      第57回日本ウイルス学会学術集会
    • Place of Presentation
      東京
    • Year and Date
      2009-10-26
    • Related Report
      2009 Annual Research Report
  • [Presentation] GFP発現組換えマウスサイトメガロウイルスを用いた in vivo imaging による抗ヘルペスウイルス薬 in vivo 評価系の確立2009

    • Author(s)
      山田壮一, 小杉伊三夫, 片野晴隆, 倉根一郎, 井上直樹
    • Organizer
      第57回日本ウイルス学会学術集会
    • Place of Presentation
      東京
    • Year and Date
      2009-10-26
    • Related Report
      2009 Annual Research Report
  • [Presentation] サイトメガロウイルス感染モデルマウスを用いた聴覚障害機序の解析2009

    • Author(s)
      生田和史, 小川洋, 大森孝一, 小杉伊三夫, 新井義文, 錫谷達夫
    • Organizer
      第57回日本ウイルス学会学術集会
    • Place of Presentation
      東京
    • Year and Date
      2009-10-26
    • Related Report
      2009 Annual Research Report
  • [Presentation] 発育期大脳神経細胞におけるマウスサイトメガロウイルス感染と脳障害発症機構の解析2009

    • Author(s)
      小杉伊三夫
    • Organizer
      第24回ヘルペスウイルス研究会
    • Place of Presentation
      裾野
    • Year and Date
      2009-07-02
    • Related Report
      2010 Final Research Report
  • [Presentation] Differential activation of murine cytomegalovirus el promoter in neurons during infection of the developing mouse brain and primary neuronal culture2009

    • Author(s)
      小杉伊三夫, 河崎秀陽, 新井義文, 筒井祥博
    • Organizer
      第12回国際サイトメガロウイルスワークショップ
    • Place of Presentation
      ボストン、米国
    • Year and Date
      2009-05-11
    • Related Report
      2009 Annual Research Report
  • [Presentation] 発育期大脳神経細胞におけるサイトメガロウイルス持続感染と脳障害発症機構の解析2009

    • Author(s)
      小杉伊三夫
    • Organizer
      第98回日本病理学会総会
    • Place of Presentation
      京都
    • Year and Date
      2009-05-01
    • Related Report
      2010 Final Research Report
  • [Presentation] 発育脳神経細胞におけるサイトメガロウイルス感染と脳発達障害2009

    • Author(s)
      小杉伊三夫, 河崎秀陽, 新井義文, 筒井祥博
    • Organizer
      第98回日本病理学会総会
    • Place of Presentation
      京都
    • Year and Date
      2009-05-01
    • Related Report
      2009 Annual Research Report
  • [Presentation] Differential activation of murine cytomegalovirus el promoter in neurons during infection of the developing mouse brain and primary neuronal culture2009

    • Author(s)
      Isao Kosugi, Yoshifumi Arai, Hideya Kawasaki, Yoshihiro Tsutsui
    • Organizer
      第12回国際サイトメガロウイルスワークショップ
    • Place of Presentation
      米国
    • Related Report
      2010 Final Research Report
  • [Presentation] 発育期大脳神経細胞におけるマウスサイトメガロウイルス感染と脳障害発症機構の解析2008

    • Author(s)
      小杉伊三夫
    • Organizer
      第56回日本ウイルス研究会
    • Place of Presentation
      岡山
    • Year and Date
      2008-10-26
    • Related Report
      2010 Final Research Report
  • [Presentation] 発育脳におけるマウスサイトメガロウイルスの臨界期神経細胞に特異的な感染動態2008

    • Author(s)
      小杉伊三夫, 河崎秀陽, 新井義文, 筒井祥博
    • Organizer
      第56回日本ウイルス学会学術集会
    • Place of Presentation
      岡山市
    • Year and Date
      2008-10-26
    • Related Report
      2008 Annual Research Report
  • [Presentation] 発育期大脳神経細胞におけるマウスサイトメガロウイルス感染と脳障害発症機構の解析2008

    • Author(s)
      小杉伊三夫
    • Organizer
      第23回ヘルペスウイルス研究会
    • Place of Presentation
      鳥取
    • Year and Date
      2008-06-10
    • Related Report
      2010 Final Research Report
  • [Presentation] 発育期脳におけるサイトメガロウイルスの神経細胞特異的な感染動態と脳発達障害2008

    • Author(s)
      小杉伊三夫, 河崎秀陽, 新井義文, 李立, 筒井祥博
    • Organizer
      第97回日本病理学会総会ワークショップ
    • Place of Presentation
      金沢市
    • Year and Date
      2008-05-17
    • Related Report
      2008 Annual Research Report
  • [Presentation] 発育期大脳神経細胞におけるサイトメガロウイルス持続感染と脳障害発症機構の解析2008

    • Author(s)
      小杉伊三夫
    • Organizer
      第97回日本病理学会総会
    • Place of Presentation
      金沢
    • Year and Date
      2008-05-12
    • Related Report
      2010 Final Research Report
  • [Presentation] A unique activation of marine cytomegalovirus el promoter in neurons during the infection of the developing mouse brain and primary neuronal culture2008

    • Author(s)
      Kosugi I, Arai Y, Kawasaki H, Li L, Tsutsui Y
    • Organizer
      第33回国際ヘルペスウイルスワークショップ
    • Place of Presentation
      ポルトガル
    • Related Report
      2010 Final Research Report
  • [Presentation] A unique activation of murine cytomegalovirus el promoter in neurons during the infection of the developing mouse brain and primary neuronal culture2008

    • Author(s)
      小杉伊三夫, 河崎秀陽, 新井義文, 李立, 筒井祥博
    • Organizer
      第33回国際ヘルペスウイルスワークショップ
    • Place of Presentation
      エストリル, ポルトガル
    • Related Report
      2008 Annual Research Report
  • [Presentation] 発育期大脳神経細胞におけるマウスサイトメガロウイルス感染と脳障害発症機構の解析

    • Author(s)
      小杉伊三夫
    • Organizer
      第57回日本ウ
    • Related Report
      2010 Final Research Report
  • [Remarks] ホームページ等

    • Related Report
      2010 Final Research Report
  • [Remarks]

    • URL

      http://www2.hama-med.ac.jp/w1a/patho2/index.htm

    • Related Report
      2010 Annual Research Report
  • [Remarks]

    • URL

      http://www2.hama-med.ac.jp/w1a/patho2/index.htm

    • Related Report
      2009 Annual Research Report
  • [Remarks]

    • URL

      http://www2.hama-med.ac.jp/wla/patho2/index.htm

    • Related Report
      2008 Annual Research Report

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Published: 2008-04-01   Modified: 2016-04-21  

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