Exhaustive analysis of molecular mechanism of EB virus reactivation

• Project/Area Number: 20790362
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Single-year Grants
• Research Field: Virology
• Research Institution: Aichi Cancer Center Research Institute
• Principal Investigator: MURATA Takayuki Aichi Cancer Center Research Institute, 腫瘍ウイルス学部, 研究員 (30470165)
• Project Period (FY): 2008 – 2009
• Project Status: Completed (Fiscal Year 2009)
• Budget Amount: ¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000); Fiscal Year 2009: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000); Fiscal Year 2008: ¥2,470,000 (Direct Cost: ¥1,900,000、Indirect Cost: ¥570,000)
• Keywords: EBウイルス / 再活性化 / TORC2

Research Abstract

本研究では、伝染性単核球症を引き起こし、バーキットリンパ腫、胃癌などの癌の原因にもなるEpstein-Barr virus(EBウイルス)のライフサイクル解明のため、特にウイルスの潜伏感染からの再活性化のメカニズムに焦点をおいて研究を開始した。このような詳細なウイルスライフサイクルの解明はウイルス拡散防止に役立つ点で意義深い研究である。研究は順調に進行した。我々が新規に見いだした遺伝子による再活性化調節についてすでに学術雑誌に報告した(Murata et al.,JBC(2009)284:8033-41)ほか、cDNA ライブラリを用いたファンクショナルスクリーニングとその後の詳細な検証の結果、非常にインパクトのある因子を明らかにし、現在投稿準備中である。

Research Products

• [Journal Article] Transient increases in p53-responsible gene expression at early stages of Epstein-Barr virus productive replication. (2010)
  • Author(s): Sato Y, Shirata N, Murata T, Nakasu S, Kudoh A, Iwahori S, Nakayama S, Chiba S, Isomura H, Kanda T, Tsurumi T.
  • Journal Title: Cell Cycle 9(4) Pages: 807-14
  • Peer Reviewed
• [Journal Article] Degradation of phosphorylated p53 by viral protein-ECS E3 ligase complex. (2009)
  • Author(s): Sato Y, Kamura T, Shirata N, Murata T, Kudoh A, Iwahori S, Nakayama S, Isomura H, Nishiyama Y, Tsurumi T.
  • Journal Title: PLoS Pathog 5(7)(in press)
  • Peer Reviewed
• [Journal Article] Epstein-Barr virus polymerase processivity factor enhances BALF2 promoter transcription as a coactivator for the BZLF1 immediate-early protein. (2009)
  • Author(s): Nakayama S, Murata T, Murayama K, Yasui Y, Sato Y, Kudoh A, Iwahori S, Isomura H, Kanda T, Tsurumi T.
  • Journal Title: J Biol Chem. 284(32) Pages: 21557-68
  • Peer Reviewed
• [Journal Article] Phosphorylation of p27Kip1 by Epstein-Barr virus protein kinase induces its degradation through SCFSkp2 ubiquitin ligase actions during viral lytic replication. (2009)
  • Author(s): Iwahori S, Murata T, Kudoh A, Sato Y, Nakayama S, Isomura H, Kanda T, Tsurumi T.
  • Journal Title: J Biol Chem. 284(28) Pages: 18923-31
  • Peer Reviewed
• [Journal Article] Efficient production of infectious viruses requires enzymatic activity of Epstein-Barr virus protein kinase. (2009)
  • Author(s): Murata T, Isomura H, Yamashita Y, Toyama S, Sato Y, Nakayama S, Kudoh A, Iwahori S, Kanda T, Tsurumi T.
  • Journal Title: Virology 389(1-2) Pages: 75-81
  • Peer Reviewed
• [Journal Article] Homologous recombinational repair factors are recruited and loaded onto the viral DNA genome in Epstein-Barr virus replication compartments. (2009)
  • Author(s): Kudoh A, Iwahori S, Sato Y, Nakayama S, Isomura H, Murata T, Tsurumi T.
  • Journal Title: J Virol. 83(13) Pages: 6641-51
  • Peer Reviewed
• [Journal Article] TORC2, a coactivator of cAMP-response element-binding protein, promotes Epstein-Barr virus reactivation from latency through interaction with viral BZLF1 protein. (2009)
  • Author(s): Murata T, Sato Y, Nakayama S, Kudoh A, Iwahori S, Isomura H, Tajima M, Hishiki T, Ohshima T, Hijikata M, Shimotohno K, Tsurumi T.
  • Journal Title: J Biol Chem. 284(12) Pages: 8033-41
  • Peer Reviewed
• [Journal Article] Efficient production of infectious viruses requires enzymatic activity of Epstein-Barr virus protein kinase (2009)
  • Author(s): Murata T
  • Journal Title: Virology 389 Pages: 75-81
  • Peer Reviewed
• [Journal Article] Phosphorylation of p27Kip1 by Epstein-Barr virus protein kinase induces its degradation through SCFSkp2 ubiquitin ligase actions during viral lytic replication (2009)
  • Author(s): Iwahori s
  • Journal Title: J Biol Chem 284 Pages: 18923-18931
  • Peer Reviewed
• [Journal Article] Epstein-Barr virus polymerase processivity factor enhances BALF2 promoter transeription as a coactivator for the BZLF1 immediate-early protein (2009)
  • Author(s): Nakayama S
  • Journal Title: J Biol Chem 284 Pages: 21557-21568
  • Peer Reviewed
• [Journal Article] TORC2, a Coactivator of cAMP-response Element-binding Protein, Promotes Epstein-Barr Virus Reactivation from Latency through Interaction with Viral BZLF1 Protein (2009)
  • Author(s): Murata T
  • Journal Title: J Biol Chem 284(12) Pages: 8033-8041
  • Peer Reviewed
• [Journal Article] Identification of phosphorylation sites on transcription factor Sp1 in response to DNA damage and its accumulation at damaged sites (2008)
  • Author(s): Iwahori S
  • Journal Title: Cell Signal 20(10) Pages: 1795-1803
  • Peer Reviewed
• [Presentation] TOR2はBZLF1と共同してEBウイルスの再活性化を促進する (2009)
  • Author(s): 村田貴之, 鶴見達也
  • Organizer: 第67回日本癌学会学術集会
  • Place of Presentation: 名古屋
  • Year and Date: 2009-10-29
• [Presentation] EBウイルスの再活性化-EBウイルスBZLF1遺伝子はSUMO化によりその転写活性を抑制される (2009)
  • Author(s): 村田貴之, 鶴見達也
  • Organizer: 第57回日本ウイルス学会学術集会
  • Place of Presentation: 東京
  • Year and Date: 2009-10-27
• [Presentation] EBウイルスの再活性化-TOR2はBZLF1遺伝子と共同してEBウイルスの再活性化を促進する (2009)
  • Author(s): 村田貴之, 鶴見達也
  • 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
• [Presentation] Epstein-BarrウイルスBZLF1遺伝子産物はSUMO化によりその転写活性を強く抑制される (2009)
  • Author(s): 村田貴之, 鶴見達也
  • Organizer: 第68回日本癌学会学術総会
  • Place of Presentation: 横浜
  • Year and Date: 2009-10-01
• [Presentation] TORC2 promotes EBV reactivation from latency through interaction with viral BZLF1 protein (2009)
  • Author(s): Murata T, Tsurumi T.
  • Organizer: 第四回上咽頭がん国際シンポジウム
  • Place of Presentation: マラケシュ(モロッコ)
  • Year and Date: 2009-06-19
• [Presentation] (2009)
  • Author(s): 村田貴之
  • Organizer: 第4回上咽頭がん国際シンポジウム
  • Place of Presentation: マラケシュ(モロッコ)
  • Year and Date: 2009-06-19
• [Presentation] Calcineurin Promotes EBV Reactivation from Latency via TORC2 (2008)
  • Author(s): 村田貴之
  • Organizer: 8th International Conference on Protein Phosphatase
  • Place of Presentation: Maebashi
  • Year and Date: 2008-11-12
• [Presentation] TORC2 promotes EBV reactivation from latency by interacting with BZLF1 (2008)
  • Author(s): 村田貴之
  • Organizer: 第67回日本癌学会学術総会
  • Place of Presentation: 名古屋
  • Year and Date: 2008-10-29
• [Remarks]
  • URL: http://www.pref.aichi.jp/cancer-center/400/420/421/421-06.html