Construction of novel platforms for herpes simplex virus attenuated vaccines

• Project/Area Number: 26670220
• Research Category: Grant-in-Aid for Challenging Exploratory Research
• Allocation Type: Multi-year Fund
• Research Field: Virology
• Research Institution: The University of Tokyo
• Principal Investigator: Kawaguchi Yasushi 東京大学, 医科学研究所, 教授 (60292984)
• Project Period (FY): 2014-04-01 – 2017-03-31
• Project Status: Completed (Fiscal Year 2016)
• Budget Amount: ¥3,640,000 (Direct Cost: ¥2,800,000、Indirect Cost: ¥840,000); Fiscal Year 2015: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000); Fiscal Year 2014: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
• Keywords: HSV / 宿主免疫回避 / 感染制御 / 制御

Outline of Final Research Achievements

We have constructed novel live attenuated herpes simplex virus (HSV) vaccines. The constructed vaccines exhibited more vaccine efficacy than a control live attenuated HSV vaccine, TK-deficient mutant virus. In addition, we identified novel HSV proteins that inhibit host immune responses. One of the HSV proteins inhibited induction of proinfalamatory cytokines, which are known to control HSV infection in vivo, by interacting with a host cellular protein that regulates the induction of the proinflamatory cytokines.

Research Products

• [Journal Article] p53 is a Host Cell Regulator during Herpes Simplex Encephalitis. (2016)
  • Author(s): Maruzuru Y, Koyanagi N, Takemura N, Uematsu S, Matsubara D, Suzuki Y, Arii J, Kato A, Kawaguchi Y.
  • Journal Title: J Virol. Volume: 90(15) Issue: 15 Pages: 6738-6745
  • DOI: 10.1128/jvi.00846-16
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Characterization of a Herpes Simplex Virus 1 (HSV-1) Chimera in Which the Us3 Protein Kinase Gene Is Replaced with the HSV-2 Us3 Gene. (2015)
  • Author(s): Shindo K, Kato A, Koyanagi N, Sagara H, Arii J, Kawaguchi Y.
  • Journal Title: J Virol. Volume: 90 Issue: 1 Pages: 457-473
  • DOI: 10.1128/jvi.02376-15
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Phosphorylation of Herpes Simplex Virus 1 dUTPase Regulates Viral Virulence and Genome Integrity by Compensating for Low Cellular dUTPase Activity in the Central Nervous System. (2015)
  • Author(s): A. Kato, J. Arii, Y. Koyanagi, and Y. Kawaguchi.
  • Journal Title: Journal of Virology Volume: 89 Issue: 1 Pages: 241-8
  • DOI: 10.1128/jvi.02497-14
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Phosphorylation of Herpes Simplex Virus 1 dUTPase Up-regulated Viral dUTPase Activity to Compensate for Low Cellular dUTPase Activity for Efficient Viral Replication. (2014)
  • Author(s): A. Kato, Y. Hirohata, J. Arii, and Y. Kawaguchi.
  • Journal Title: Journal of Virology Volume: 88 Issue: 14 Pages: 7776-85
  • DOI: 10.1128/jvi.00603-14
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Presentation] p53はHSV-1の神経病原性に関与する (2016)
  • Author(s): 丸鶴雄平, 小栁直人, 有井潤, 加藤哲久, 川口寧
  • Organizer: 第30回ヘルペスウイルス研究会
  • Place of Presentation: セミナーハウス クロス・ウェーブ府中（東京都府中市）
  • Year and Date: 2016-06-16
• [Presentation] Elucidation of the type-specific differences in herpes simplex virus Us3 genes. (2015)
  • Author(s): Keiko Shindo, Akihisa Kato, Koyanagi Naoto, Jun Arii, Yasushi Kawaguchi.
  • Organizer: The 14th Awaji International Forum on Infection and Immunity
  • Place of Presentation: 淡路夢舞台国際会議場（兵庫県淡路市）
  • Year and Date: 2015-09-08
  • Int'l Joint Research
• [Presentation] 中枢神経系における新規HSV-1宿主免疫回避機構の解明：HSV-1プロテインキナーゼUL13はCXCL9の発現を抑制し、中枢神経系へのCD8+ T細胞の浸潤を阻害する (2014)
  • Author(s): 小栁直人、 今井孝彦、 神道慶子、有井 潤、加藤哲久、川口 寧
  • Organizer: 第62回日本ウイルス学会学術集会
  • Place of Presentation: 横浜
  • Year and Date: 2014-11-10 – 2014-11-12
• [Presentation] The HSV-1 UL13 protein kinase down-regulates expression of a cytokine to inhibit CD8+ T cell infiltration into the central nervous system. (2014)
  • Author(s): Naoto Koyanagi, Takahiko Imai, Keiko Shindo, Jun Arii, Akihisa Kato and Yasushi Kawaguchi
  • Organizer: 39th Annual International Herpesvirus Workshop.
  • Place of Presentation: Kobe, Japan
  • Year and Date: 2014-07-19 – 2014-07-23
• [Presentation] Characterization of a recombinant chimera HSV-1 in which its Us3 gene is substituted with the HSV-2 Us3 gene. (2014)
  • Author(s): Keiko Shindo, Jun Arii, Akihisa Kato and Yasushi Kawaguchi.
  • Organizer: 39th Annual International Herpesvirus Workshop.
  • Place of Presentation: Kobe, Japan
  • Year and Date: 2014-07-19 – 2014-07-23
• [Remarks] 東京大学医科学研究所 感染・免疫部門 ウイルス病態制御分野
  • URL: http://www.ims.u-tokyo.ac.jp/Kawaguchi-lab/KawaguchiLabTop.html
• [Remarks] 東京大学医科学研究所感染免疫部門ウイルス病態制御分野
  • URL: http://www.ims.u-tokyo.ac.jp/Kawaguchi-lab/KawaguchiLabTop.html