Studies on the immunoinhibitory mechanisms of Marek's disease virus and its application for adjuvant

• Project/Area Number: 23380176
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Applied veterinary science
• Research Institution: Hokkaido University
• Principal Investigator: OHASHI KAZUHIKO 北海道大学, (連合)獣医学研究科, 教授 (90250498)
• Co-Investigator(Kenkyū-buntansha): KONNAI Satoru 北海道大学, 大学院・獣医学研究科, 准教授 (40396304) ; 村田 史郎 北海道大学, (連合)獣医学研究科, 助教 (10579163)
• Co-Investigator(Renkei-kenkyūsha): MURATA Shiro 北海道大学, 大学院・獣医学研究科, 助教 (10579163)
• Project Period (FY): 2011-04-01 – 2014-03-31
• Project Status: Completed (Fiscal Year 2013)
• Budget Amount: ¥18,460,000 (Direct Cost: ¥14,200,000、Indirect Cost: ¥4,260,000); Fiscal Year 2013: ¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000); Fiscal Year 2012: ¥5,980,000 (Direct Cost: ¥4,600,000、Indirect Cost: ¥1,380,000); Fiscal Year 2011: ¥7,540,000 (Direct Cost: ¥5,800,000、Indirect Cost: ¥1,740,000)
• Keywords: マレック病 / マレック病ウイルス / 免疫抑制 / PD-1 / 獣医学 / 免疫抑制因子

Research Abstract

The programmed death 1 (PD-1) receptor and its ligands, programmed death ligand 1 (PD-L1) and 2 (PD-L2) are known to have an immunoinhibitory function which contribute to the pathogenesis of chronic infections and neoplastic diseases via the PD-1/PD-L pathway. In this study, it has been shown that chicken PD-1 and PD-L1/PD-L2 also have an immunoinhibitory function, such as inhibition of cytokine production. The expressions of PD-1 and PD-L2 were significantly higher in the spleens of infected chickens in the latent phase and in tumor lesions caused by Marek's disease virus (MDV). These results suggest that chicken PD-1/PD-L2 pathway is involved in the establishment of latency and tumor formation by MDV.

Research Products

• [Journal Article] Expression analysis of programmed death ligand 2 in tumors caused by the avian oncovirus Marek's disease virus (2014)
  • Author(s): Matsuyama-Kato, A., Murata, S., Isezaki, M., Takasaki, S., Kano, R., Konnai, S., & Ohashi, K
  • Journal Title: Arch. Virol Volume: (印刷中) Issue: 8 Pages: 2123-6
  • DOI: 10.1007/s00705-014-2021-7
  • Peer Reviewed
• [Journal Article] Influence of PD-L1 cross-linking on cell death in PD-L1-expressing cell lines and bovine lymphocytes (2014)
  • Author(s): Ryoyo Ikebuchi, Satoru Konnai, Tomohiro Okagawa, Kazumasa Yokoyma, Chie Nakajima, Yasuhiko Suzuki, Shiro Murata, Kazuhiko Ohashi.
  • Journal Title: Immunology Volume: (印刷中) Issue: 4 Pages: 551-61
  • DOI: 10.1111/imm.12243
  • Peer Reviewed
• [Journal Article] Characterization of Meq proteins from field isolates of Marek’s disease virus in Japan (2013)
  • Author(s): Murata, S., Hashiguchi, T., Hayashi, Y., Yamamoto, Y., Matsuyama-Kato, A., Takasaki, S., Isezaki, M., Onuma, M., Konnai, S., Ohashi, K.
  • Journal Title: Infect Genet Evol. Volume: 16C Pages: 137-143
  • DOI: 10.1016/j.meegid.2012.12.032
  • NAID: 120005317003
  • Peer Reviewed
• [Journal Article] Enhanced expression of LAG-3 on lymphocyte subpopulations from persistently lymphocytotic cattle infected with bovine leukemia virus (2013)
  • Author(s): Konnai, S., Suzuki, S., Shirai, T., Ikebuchi, R., Okagawa, T., Sunden., Y, Mingala C.N., Onuma, M., Murata, S., Ohashi K.
  • Journal Title: Comp Immunol Microbiol Infect Dis. Volume: 36 Issue: 1 Pages: 63-9
  • DOI: 10.1016/j.cimid.2012.09.005
  • Peer Reviewed
• [Journal Article] Blockade of bovine PD-1 increases T cell function and inhibits bovine leukemia virus expression in B cells in vitro (2013)
  • Author(s): Ryoyo Ikebuchi, Satoru Konnai, Tomohiro Okagawa, Kazumasa Yokoyma, Chie Nakajima, Yasuhiko Suzuki, Shiro Murata, Kazuhiko Ohashi.
  • Journal Title: Veterinary Research Volume: 44 Issue: 1 Pages: 59-59
  • DOI: 10.1186/1297-9716-44-59
  • Peer Reviewed
• [Journal Article] Expression analysis of Foxp3 in T cells from bovine leukemia virus infected cattle (2013)
  • Author(s): Saori Suzuki, Satoru Konnai, Tomohiro Okagawa, Ryoyo Ikebuchi, Tatsuya Shirai, Yuji Sunden, Claro N. Mingala, Shiro Murata, Kazuhiko Ohashi
  • Journal Title: Microbiology and Immunology Volume: 57 Pages: 600-604
  • DOI: 10.1111/j.1348-0421.12073
  • Peer Reviewed
• [Journal Article] Molecular characterization of immunoinhibitory factors PD-1/PD-L1 in chickens infected with Marek's disease virus (2012)
  • Author(s): Matsuyama-Kato, A., Murata, S., Isezaki, M., Kano, R., Takasaki, S., Ichii, O., Konnai, S., & Ohashi, K
  • Journal Title: Virol. J Volume: 9 Issue: 1 Pages: 94-94
  • DOI: 10.1186/1743-422x-9-94
  • Peer Reviewed
• [Journal Article] Increased bovine Tim-3 and its ligand expressions during bovine leukemia virus infection (2012)
  • Author(s): Okagawa, T., Konnai, S., Ikebuchi, R., Suzuki, S., Shirai, T., Sunden, Y., Onuma M., Murata, S., Ohashi, K.
  • Journal Title: Vet. Res. Volume: 43 Issue: 1 Pages: 45-45
  • DOI: 10.1186/1297-9716-43-45
  • Peer Reviewed
• [Journal Article] Surveillance or Marek's disease virus in migratory and sedentary birds in Hokkaido, Japan (2011)
  • Author(s): Murata S., et al.
  • Journal Title: Veterinary Journal Volume: 192(印刷中) Issue: 3 Pages: 538-540
  • DOI: 10.1016/j.tvjl.2011.07.006
  • Peer Reviewed
• [Journal Article] Analysis of transcriptional activities of the Meq proteins present in highly virulent Marek's disease virus strains, RB1B and Md5 (2011)
  • Author(s): Murata S., et al.
  • Journal Title: Virus Genes Volume: 43 Issue: 1 Pages: 66-71
  • DOI: 10.1007/s11262-011-0612-x
  • Peer Reviewed
• [Journal Article] Increase of cells expressing PD-L1 in bovine leukemia virus infection and enhancement of anti-viral immune responses in vitro via PD-L1 blockade (2011)
  • Author(s): R.Ikebuchi, S.Konnai, T.Shirai, Y.Sunden, S.Murata, M.Onuma, K.Ohashi
  • Journal Title: Veterinary Research Volume: 42 Issue: 1 Pages: 103-103
  • DOI: 10.1186/1297-9716-42-103
  • Peer Reviewed
• [Journal Article] Molecular cloning of bovine lymphocyte activation gene-3 and its expression characteristics in bovine leukemia virus-infected cattle (2011)
  • Author(s): Shirai T, Konnai S, Ikebuchi R, Okagawa T, Suzuki S, Sunden Y, Onuma M, Murata S, Ohashi K
  • Journal Title: Vet.Immunol.Immunopathol. Volume: 44 Issue: 3-4 Pages: 462-467
  • DOI: 10.1016/j.vetimm.2011.08.018
  • Peer Reviewed
• [Journal Article] マガンなどの野生水禽の疾病抵抗性とマレック病ウイルスの分布 (2011)
  • Author(s): 大橋和彦, 松原綾子, 村田史郎, 今内覚
  • Journal Title: J. V. M Volume: 64 Pages: 21-26
  • URL: http://iss.ndl.go.jp/books/R100000002-I000000010707-00
• [Presentation] マレック病腫瘍病変形成における免疫抑制因子発現機序の検討 (2013)
  • Author(s): 松山あゆ美, 村田史郎, 伊勢崎政美, 今内覚, 大橋和彦
  • Organizer: 第156回日本獣医学会学術集会
  • Place of Presentation: 岐阜大学(岐阜)
  • Year and Date: 2013-09-20
• [Presentation] マレック病腫瘍病変形成における免疫抑制因子発現機序の検討 (2013)
  • Author(s): 松山 あゆ美、村田 史郎、伊勢崎 政美、今内 覚、大橋 和彦
  • Organizer: 第156回日本獣医学会学術集会
  • Place of Presentation: 岐阜大学（岐阜県）
• [Presentation] マレック病感染鶏由来腫瘍病変部における免疫抑制因子PD-1/PD-L 発現の形態学的解析 (2012)
  • Author(s): 村田史郎, 松山あゆ美, 伊勢崎政美, 高崎紗蘭, 市居修, 今内覚, 大橋和彦
  • Organizer: 第154回日本獣医学会学術集会
  • Place of Presentation: 岩手大学(盛岡)
  • Year and Date: 2012-09-16
• [Presentation] マレック病ウイルスワクチン接種鶏における免疫抑制因子PD-1 およびPD-L1 の発現解析 (2012)
  • Author(s): 高崎紗蘭, 村田史郎, 松山あゆ美, 伊勢崎政美, 今内覚, 大橋和彦
  • Organizer: 第154回日本獣医学会学術集会
  • Place of Presentation: 岩手大学(盛岡)
  • Year and Date: 2012-09-16
• [Presentation] Characterization of Meq proteins from field isolates of Mrek's disease virus in Japan (2012)
  • Author(s): Murata, S., Hashiguchi, T., Hayashi, Y., Yamamoto, Y., Kato, A., Takasaki, S., Isezaki, M., Konnai, S., & Ohashi, K
  • Organizer: 9th International Symposium on Marek's Disease and Avian Herpesviruses
  • Place of Presentation: Berlin, Germany
  • Year and Date: 2012-06-24
• [Presentation] Characterization of immunoinhibitory factors PD-1/PD-L1 in chickens infected with Marek's disease virus (2012)
  • Author(s): Matsuyama-Kato, A., Murata, S., Isezaki, M., Kano, R., Takasaki, S., Ichii, O., Konnai, S., & Ohashi, K
  • Organizer: 9th International Symposium on Marek's Disease and Avian Herpesviruses
  • Place of Presentation: Berlin, Germany
  • Year and Date: 2012-06-24
• [Presentation] マレック病感染鶏由来腫瘍病変部における免疫抑制因子PD-1/PD-L1発現の形態学的解析 (2012)
  • Author(s): 村田史郎
  • Organizer: 日本獣医学会学術集会
  • Place of Presentation: 岩手大学(盛岡市)
• [Presentation] マレック病ウイルスワクチン接種鶏における免疫抑制因子PD-1およびPD-L1の発現解析 (2012)
  • Author(s): 髙﨑紗蘭
  • Organizer: 日本獣医学会学術集会
  • Place of Presentation: 岩手大学(盛岡市)
• [Presentation] マレック病ウイルス強毒株由来Meq および弱毒株由来L-Meq によるbcl-2 遺伝子発現調節の比較 (2011)
  • Author(s): 村田史郎, 伊勢崎政美, 松山あゆ美, 高崎紗蘭, 今内覚, 大橋和彦
  • Organizer: 第152回日本獣医学会学術集会
  • Place of Presentation: 大阪府立大学(堺)
  • Year and Date: 2011-09-20
• [Presentation] Amino acid substitutions or insertion in the Meq proteins could affect their transactivation and transformation abilities (2011)
  • Author(s): Murata, S., Hashiguchi, T., Okada, T., Kano, R., Onuma, M., Konnai, S., & Ohashi, K
  • Organizer: International Union of Microbiological Societies Congress
  • Place of Presentation: Sapporo, Japan
  • Year and Date: 2011-09-11