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

2013 Fiscal Year Final Research Report

• 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)
• 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
• Keywords: マレック病 / マレック病ウイルス / 免疫抑制 / PD-1

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)
  • 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): Ikebuchi, R., Konnai, S., Okagawa, T., Yokoyama, K., Nakajima, C., Suzuki, Y., Murata, S., & Ohashi, K
  • Journal Title: Immunology Volume: (印刷中)
  • 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: 16 Pages: 137-143
  • DOI: 10.1016/j.meegid.2012.12.032
  • 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 Pages: 63-69
  • 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): Ikebuchi., R., Konnai, S., Okagawa, T., Yokoyama, K., Nakajima, C., Suzuki, Y., Murata, S., & Ohashi, K
  • Journal Title: Vet. Res Volume: 44 Pages: 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): Suzuki, S., Konnai, S., Okagawa, T., Ikebuchi, R., Shirai, T., Sunden, Y., Mingala, C.N., Murata, S., & Ohashi, K
  • Journal Title: Microbiol. Immunol 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 Pages: 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 Pages: 45
  • DOI: 10.1186/1297-9716-43-45
  • Peer Reviewed
• [Journal Article] Surveillance of Marek's disease virus in migratory and sedentary birds in Hokkaido (2011)
  • Author(s): Murata, S., Hayashi, Y., Kato, A., Isezaki, M., Takasaki, S., Onuma, M., Osa, Y., Asakawa, M., Konnai, S., & Ohashi, K
  • Journal Title: Japan. Vet. J Volume: 192 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., Konnai, S., & Ohashi, K
  • Journal Title: Virus genes Volume: 43 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): Ikebuchi, R., Konnai, S., Shirai, T., Sunden, Y., Murata, S., Onuma, M., & Ohashi, K
  • Journal Title: Vet. Res Volume: 42 Pages: 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: 144 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