Cis/Trans-acting elements that regulate EBV reactivation from latency and epigenetics

• Project/Area Number: 24590566
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Virology
• Research Institution: Nagoya University (2013-2014); 愛知県がんセンター(研究所) (2012)
• Principal Investigator: MURATA Takayuki 名古屋大学, 医学(系)研究科(研究院), 准教授 (30470165)
• Project Period (FY): 2012-04-01 – 2015-03-31
• Project Status: Completed (Fiscal Year 2014)
• Budget Amount: ¥5,330,000 (Direct Cost: ¥4,100,000、Indirect Cost: ¥1,230,000); Fiscal Year 2014: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2013: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2012: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
• Keywords: 再活性化

Outline of Final Research Achievements

We here analyzed the molecular mechanisms that govern reactivation of Epstein-Barr virus (EBV) from latency. Research like this is of significance, because EBV reactivation contributes not only to virus spreading but also to pathogenesis of EBV-related cancers.
Reactivation of EBV is dependent on the expression of viral immediate-early gene, BZLF1. We thus analyzed the promoter region of BZLF1 gene. Through exhaustive functional cloning, we here identified host factors that can induce EBV reactivation, and even more, we observed epigenetic modification of the promoter that associates with reactivation.

Research Products

• [Journal Article] Switching of EBV cycles between latent and lytic states (2014)
  • Author(s): Murata T, Tsurumi T.
  • Journal Title: Rev Med Virol. Volume: 24 Issue: 3 Pages: 142-153
  • DOI: 10.1002/rmv.1780
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Modes of infection and oncogenesis by the Epstein-Barr virus (2014)
  • Author(s): Murata T, Sato Y, Kimura H.
  • Journal Title: Rev Med Virol. Volume: 24 Issue: 4 Pages: 242-253
  • DOI: 10.1002/rmv.1786
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Contribution of Myocyte Enhancer Factor 2 (MEF2) Family Transcription Factors to BZLF1 Expression in Epstein-Barr virus Reactivation from Latency. (2013)
  • Author(s): Murata T, Narita Y, Sugimoto A, Kawashima D, Kanda T, Tsurumi T
  • Journal Title: Journal of Virology Volume: 87 Issue: 18 Pages: 10148-10162
  • DOI: 10.1128/jvi.01002-13
  • Peer Reviewed
• [Journal Article] Epstein-Barr virus deubiquitinase downregulates TRAF6-mediated NF-κB signaling during productive replication. (2013)
  • Author(s): Saito S, Murata T, Kanda T, Isomura H, Narita Y, Sugimoto A, Kawashima D, Tsurumi T.
  • Journal Title: Journal of Virology Volume: 87 Issue: 7 Pages: 4060-4070
  • DOI: 10.1128/jvi.02020-12
  • Peer Reviewed
• [Journal Article] Epigenetic histone modification of Epstein-Barr virus BZLF1 promoter during latency and reactivation in Raji cells. (2012)
  • Author(s): Murata T.
  • Journal Title: J Virol. Volume: 86(9) Issue: 4 Pages: 4752-61
  • DOI: 10.1128/jvi.02634-12
  • Peer Reviewed
• [Presentation] EBV BGLF3.5遺伝子欠損株の性状解析 (2014)
  • Author(s): 村田貴之、五島典、木村宏
  • Organizer: 第62回日本ウイルス学会学術集会
  • Place of Presentation: パシフィコ横浜（神奈川県横浜市）
  • Year and Date: 2014-11-10 – 2014-11-12
• [Presentation] Contribution of MEF2 family transcription factors to BZLF1 expression in EBV reactivation from latency (2014)
  • Author(s): Murata T, Kimura H, Tsurumi T
  • Organizer: International Union of Microbiological Societies Congress
  • Place of Presentation: Montreal（Canada）
  • Year and Date: 2014-07-27 – 2014-08-01
• [Presentation] EBウイルスの感染様式とがん化 (2013)
  • Author(s): 村田貴之、鶴見達也
  • Organizer: 日本癌学会学術総会
  • Place of Presentation: パシフィコ横浜（横浜市）
  • Invited
• [Presentation] EBV潜伏/再活性化におけるMEF2ファミリー転写因子の重要性 (2013)
  • Author(s): 村田貴之、木村宏、鶴見達也
  • Organizer: 日本ウイルス学会
  • Place of Presentation: 神戸国際会議場（神戸市）
• [Presentation] Modification of Immune/Inflammatory System by EBV and Its Contribution to Cancer
  • Author(s): Murata T
  • Organizer: 3rd International Symposium on Carcinogenic Spiral and International Symposium on Tumor Biology in Kanazawa
  • Place of Presentation: 金沢エクセルホテル東急（金沢）
• [Presentation] EBV再活性化におけるエピジェネティックヒストン修飾
  • Author(s): 村田貴之
  • Organizer: 第71回日本ウイルス学会学術集会
  • Place of Presentation: 大阪国際会議場（大阪）
• [Presentation] Cis- and trans-elements that affect reactivation of Epstein-Barr virus from latency
  • Author(s): Murata T
  • Organizer: International Congress on Oncogenic Herpesviruses and Associated Diseases
  • Place of Presentation: Sheraton Philadelphia Downtown Hotel (Philadelphia)
• [Remarks] 愛知県がんセンター研究所腫瘍ウイルス学部
  • URL: http://www.pref.aichi.jp/cancer-center/ri/01bumon/06shuyo_uirusu/index.html