Diagnosis and pathogenetic analysis using a novel identification method for EBV-infected cells

• Project/Area Number: 21591384
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Pediatrics
• Research Institution: Nagoya University
• Principal Investigator: KIMURA Hiroshi 名古屋大学, 大学院・医学系研究科, 准教授 (30303621)
• Co-Investigator(Kenkyū-buntansha): ITO Yoshinori 名古屋大学, 医学部附属病院, 講師 (20373491)
• Project Period (FY): 2009 – 2011
• Project Status: Completed (Fiscal Year 2011)
• Budget Amount: ¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000); Fiscal Year 2011: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2010: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2009: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
• Keywords: 小児感染症学 / EBV / FISH / in situ hybridization / 移植後リンパ増殖症 / 感染細胞 / 慢性活動性EBV感染症 / γδT細胞 / 種痘様水疱症

Research Abstract

To diagnose Epstein Barr virus(EBV)-associated diseases and to explore the pathogenesis of EBV infection, not only must the EBV load be measured, but EBV-infected cells must also be identified. We established a novel flow cytometric in situ hybridization assay to detect EBER and surface antigen in EBV-infected cells using an EBV-encoded small RNA(EBER) specific peptide nucleic acid probe, and showed that this assay was useful for the diagnosis and decision of treatment against EBV-associated T/NK lymphoproliferative diseases such as chronic active EBV infection or post transplant lymphoproliferative disorders.

Research Products

• [Journal Article] Replication of Epstein-Barr virus primary infection in human tonsil tissue explants (2011)
  • Author(s): Gotoh K, Ito Y, Maruo S, Takada K, Mizuno T, Teranishi M, Nakata S, Nakashima T, Iwata S, Goshima F, Nakamura S, Kimura H.
  • Journal Title: PLoS One Volume: 6
  • Peer Reviewed
• [Journal Article] Identification of Epstein-Barr virus-in fected CD27+ memory B cells in patients after transplantation (2011)
  • Author(s): Ito Y, Kawabe S, Kojima S, Nakamura F, Nishiyama Y, Kaneko K, Kiuchi K, Ando H, Kimura H.
  • Journal Title: J Gen Virol Volume: 92 Pages: 2590-5
  • Peer Reviewed
• [Journal Article] Bortezomib induces apoptosis in Tlymphoma cells and natural killer lymphoma cells independent of Epstein-Barr virus infection (2011)
  • Author(s): Iwata S, Yano S, Ito Y, Ushijima Y, Gotoh K, Kawada J, Fujiwara S, Sugimoto K, Isobe Y, Nishiyama Y, Kimura H.
  • Journal Title: Int J Cancer Volume: 129 Pages: 2263-2273
  • Peer Reviewed
• [Journal Article] Kinetics of Epstein. Barrvirus load and virus-specific CD8+ Tcells in acute infectious mononucleosis (2011)
  • Author(s): Hoshino Y, Nishikawa K, Ito Y, Kuzushima K, Kimura H.
  • Journal Title: J Clin Virol Volume: 50 Pages: 244-246
  • Peer Reviewed
• [Journal Article] BortezomibはTおよびNK細胞リンパ腫にアポトーシスを惹起する (2011)
  • Author(s): 岩田誠子
  • Journal Title: Int J Cancer Volume: 129 Issue: 9 Pages: 2263-2273
  • DOI: 10.1002/ijc.25873
  • Peer Reviewed
• [Journal Article] Identification of Epstein-Barr virus-infected CD27^<+> memory B cells in patients after transplantation (2011)
  • Author(s): Ito Y
  • Journal Title: Journal of General Virology Volume: 92 Issue: 11 Pages: 2590-2595
  • DOI: 10.1099/vir.0.033712-0
  • Peer Reviewed
• [Journal Article] Replication of Epstein-Barr virus primary infection in human tonsil tissue explants (2011)
  • Author(s): Gotoh K
  • Journal Title: PLos One Volume: 6 Issue: 10 Pages: e25490-e25490
  • DOI: 10.1371/journal.pone.0025490
  • Peer Reviewed
• [Journal Article] Detection of EBV genomes in plasmablasts/plasmacells and non-B cells in the blood of most patients with EBV lympho proliferative disorders using Immuno-FISH (2010)
  • Author(s): Calatini S, Sereti I, Scheinberg P, Kimura H, Childs R, Cohen JI.
  • Journal Title: Blood Volume: 116 Pages: 4546-59
  • Peer Reviewed
• [Journal Article] Multicenter evaluation of prototype real-time PCR assays for Epstein-Barr virus and cytomegalovirus DNA in whole blood samples from transplant recipients in its current form for publication in Microbiology and Immunology (2010)
  • Author(s): Ito Y, Takakura S, Ichiyama S, Ueda M, Ando Y, Matsuda K, Hidaka E, Nakatani A, ishioka J, Nobori T, Sasaki M, Kimura H.
  • Journal Title: Microbiol Immunol Volume: 54 Pages: 516-22
  • Peer Reviewed
• [Journal Article] Immunologic and Virologic Analyses in Pediatric Liver Transplant Recipients with Chronic High Epstein-Barr Viral Loads (2010)
  • Author(s): Gotoh K, Ito Y, Ohta R, Iwata S, Nishiyama Y, Nakamura T, Kaneko K, Kiuchi T, Ando H, Kimura H.
  • Journal Title: J Infect Dis Volume: 202 Pages: 461-469
  • Peer Reviewed
• [Journal Article] Multiplex Real-time PCR Assay for Quantifying BK Polyomavirus, JC Polyomavirus, and Adenovirus DNA Simultaneously (2010)
  • Author(s): Funahashi Y, Iwata S, Ito Y, Kojima, Yoshikawa T, Hattor R, Gotoh M, Nishiyama Y, Kimura H.
  • Journal Title: J Clin Microbiol Volume: 48 Pages: 825-30
  • Peer Reviewed
• [Journal Article] Quantitative Analysis of Epstein-Barr Virus(EBV)-Related Gene Expression in Patients with Chronic Active EBV Infection (2010)
  • Author(s): Iwata S, Wada K, Tobita S, Gotoh K, Ito Y, Demachi-Okamura A, Shimizu N, Nishiyama Y, Kimura H.
  • Journal Title: J Gen Virol Volume: 90 Pages: 42-50
  • Peer Reviewed
• [Journal Article] Immunologic and Virologic Analyses in Pediatric Liver Transplant Recipients with Chronic High Epstein-Barr Viral Loads. (2010)
  • Author(s): Gotoh K
  • Journal Title: Journal of Infectious Diseases Volume: 202 Pages: 461-469
  • Peer Reviewed
• [Journal Article] Detection of EBV genomes in plasmablasts/plasma cells and non-B cells in the blood of most patients with EBV lymphoproliferative disorders using Immuno-FISH. (2010)
  • Author(s): Calatini S
  • Journal Title: Blood Volume: 116 Pages: 4546-4559
  • Peer Reviewed
• [Journal Article] Multicenter evaluation of prototype real-time PCR assays for Epstein-Barr virus and cytomegalovirus DNA in whole blood samples from transplant recipients. (2010)
  • Author(s): Ito Y
  • Journal Title: Microbiology and Immunology Volume: 54 Pages: 516-522
  • NAID: 10029545591
  • Peer Reviewed
• [Journal Article] Epstein-Barr virus AssociatedLy mphoproliferative Disease in Non-Immunocompromised Hosts (2009)
  • Author(s): Cohen JI, Kimura H, Nakamura S, Ko Y-H, Jaffe ES.
  • Journal Title: Ann Oncol Volume: 20 Pages: 1472-82
  • Peer Reviewed
• [Journal Article] Identification of Epstein-Barr virus(EBV)-infected lymphocyte subtypes by flow cytometric in situ hybridization in EBV-associated lympho proliferative diseases (2009)
  • Author(s): Kimura H, Miyake K, Yamauchi Y, Nishiyama K, Iwata S, Iwatsuki K, Gotoh K, Kojima S, Ito Y, Nishiyama Y.
  • Journal Title: J Infect Dis Volume: 200 Pages: 1078-87
  • Peer Reviewed
• [Journal Article] Cytomegalovirus and Epstein Barr virus coinfection in three toddlers with prolonged illness (2009)
  • Author(s): Ito Y, Shibata-Watanabe Y, Kawada J, Maruyama K, Yagasaki H, Kojima S, Kimura H.
  • Journal Title: J Med Virol Volume: 81 Pages: 1399-1402
  • Peer Reviewed
• [Journal Article] Multiplex real-time PCR for the simultaneous detection of her pes simplex virus (2009)
  • Author(s): Wada K, Mizoguchi S, Ito Y, Kawada J, Yamauchi Y, Morishima T, Nishiyama Y, Kimura H.
  • Journal Title: Microbiol Immunol Volume: 53 Pages: 22-29
  • Peer Reviewed
• [Journal Article] Identification of Epstein-Barr virus(EBV)-infected lymphocyte subtypes by flow cytometric in situ hybridization in EBV-associated lymphoprolifera tive diseases. (2009)
  • Author(s): Kimura H
  • Journal Title: Journal of Infectious Diseases 200 Pages: 1078-1087
  • Peer Reviewed
• [Journal Article] Epstein-Barr virus Associated Lymphoproliferative Disease in Non-Immu nocompromised Hosts. (2009)
  • Author(s): Cohen JI
  • Journal Title: Annals of Oncology 20 Pages: 1472-1482
  • Peer Reviewed
• [Presentation] EBウイルス関連T/NKリンパ増殖性疾患 (2011)
  • Author(s): 木村宏
  • Organizer: 第43回日本小児感染症学会
  • Place of Presentation: 岡山コンベンションセンター(岡山市)(招待講演)
  • Year and Date: 2011-11-29
• [Presentation] Epstein-Barr virus. Ex vivo model for Epstein-Barr virus primary infection using human tonsil tissue explants (2011)
  • Author(s): Kimura H
  • Organizer: XV International Congress of Virology
  • Place of Presentation: 札幌コンベンションセンター(札幌市)
  • Year and Date: 2011-09-12
• [Presentation] EBウイルスリンパ関連T/NKリンパ増殖性疾患 (2011)
  • Author(s): 木村宏
  • Organizer: 第43回,日本小児感染症学会、教育講演
  • Place of Presentation: 岡山
• [Presentation] Ex vivo model for Epstein-Barr virus primary infection using human tonsil tissue explants (2011)
  • Author(s): Kimura H, Gotoh K, Maruo S, Takada K, Iwata S, Goshima F, Nishiyama Y ItoY.
  • Organizer: XVI nternational Congress of Virology
  • Place of Presentation: Sapporo, Japan
• [Presentation] Noninvasive identification of EBV-infected lymphocyte subtypes in EBV-associated T/NK lymphoproliferative diseases. (2010)
  • Author(s): Kimura H
  • Organizer: The 14^<th> Biennial Conference of the International Association for Research on Epstein-Barr virus & Associated Diseases
  • Place of Presentation: Birmingham, UK.
  • Year and Date: 2010-09-07
• [Presentation] Immunologic and Virologic analyses in Pediatric Liver Transplant Recipients. Restricted EBV genome expression in pediatric liver transplant recipients with chronic high Epstein-Barr viral loads (2010)
  • Author(s): Gotoh K, Ito Y, Ohta R, Iwata S, Nishiyama Y, Kimura H.
  • Organizer: The 14^<th> Biennial Conference of the International Association for Research on Epstein-Barr virus & Associated Diseases
  • Place of Presentation: Birmingham UK
• [Presentation] No ninvasive identification of EBV-infected lymphocyte subtypes in EBV-associated T/NK lymphoproliferative diseases (2010)
  • Author(s): Kimura H, Ito Y, Kawabe S, Gotoh K, Iwata S, Nishiyama Y.
  • Organizer: The 14^<th> Biennial Conference of the International Association for Research on Epstein-Barr virus & Associated Diseases
  • Place of Presentation: Birmingham, UK
• [Presentation] FISH法を用いたEBV関連リンパ増殖性疾患の非侵襲診断および病態解析 (2009)
  • Author(s): 木村宏
  • Organizer: 第57回日本ウイルス学会学術集会
  • Place of Presentation: 東京
  • Year and Date: 2009-10-25
• [Presentation] (2009)
  • Author(s): Kimura H, Miyake K, Yamauchi Y, Iwata S, Kawabe S, Gotoh K, Ito Y
  • Organizer: The 34th International Herpesvirus Wlorkshop
  • Place of Presentation: Ithaca, USA
  • Year and Date: 2009-07-26
• [Presentation] FISH法を用いたEBV関連リンパ増殖性疾患の非侵襲診断および病態解析 (2009)
  • Author(s): 木村宏、河邊慎司、後藤研誠、伊藤嘉規、岩田誠子、西山幸廣
  • Organizer: 第57回日本ウイルス学会学術集会、ワークショップ
  • Place of Presentation: ワークショップ、東京
• [Remarks]
  • URL: http://www.med.nagoya-u.ac.jp/virus/Kimura-ebv.html
• [Remarks]
  • URL: http://www.med.nagoya-u.ac.jp/virus/Kimura-ebv.html
• [Remarks]
  • URL: http://www.med.nagoya-u.ac.jp/virus/graduate2010.html