Integrated in vivo analyses of neglected viral factors of herpes simplex virus

• Project/Area Number: 17H04080
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• 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): 2017-04-01 – 2020-03-31
• Project Status: Completed (Fiscal Year 2020)
• Budget Amount: ¥17,810,000 (Direct Cost: ¥13,700,000、Indirect Cost: ¥4,110,000); Fiscal Year 2019: ¥5,200,000 (Direct Cost: ¥4,000,000、Indirect Cost: ¥1,200,000); Fiscal Year 2018: ¥5,980,000 (Direct Cost: ¥4,600,000、Indirect Cost: ¥1,380,000); Fiscal Year 2017: ¥6,630,000 (Direct Cost: ¥5,100,000、Indirect Cost: ¥1,530,000)
• Keywords: ウイルス / HSV

Outline of Final Research Achievements

The following results were obtained for various viral factors that are non-essential genes encoded by HSV (herpes simplex virus). (i) HSV UL 13 down-regulates the response of cytotoxic T cells in vivo. (ii) Phosphorylation of UL13 at Ser-18 contributes to the regulation of the catalytic activity of UL13 and this regulation is important for efficient viral replication and pathogenesis in vivo. (iii) HSV VP22 efficiently inhibits the activation of the AIM2 inflammasome, which is important for inducing an immunoinflammatory response. (iv) HSV VP26 promotes the packaging of a viral genomic DNA into a capsid. (v) Phospho-regulation of HSV UL7 by an HSV protein kinase Us3 plays an important role in viral replication and pathogenesis in vivo.

Academic Significance and Societal Importance of the Research Achievements

様々なHSV因子の新規機能を明らかにし、それらの知見を統合的に理解することは、HSVの増殖および病態発現機構の全体像の解明に寄与するだけでなく、HSVの新たな治療法や予防法の確立に繋がると考えられる。

Research Products

• [Journal Article] Role of the DNA Binding Activity of Herpes Simplex Virus 1 VP22 in Evading AIM2-Dependent Inflammasome Activation Induced by the Virus (2020)
  • Author(s): Maruzuru Yuhei、Koyanagi Naoto、Kato Akihisa、Kawaguchi Yasushi
  • Journal Title: Journal of Virology Volume: 95 Issue: 5
  • DOI: 10.1128/jvi.02172-20
  • Peer Reviewed / Open Access
• [Journal Article] Prohibitin-1 Contributes to Cell-to-Cell Transmission of Herpes Simplex Virus 1 via the MAPK/ERK Signaling Pathway (2020)
  • Author(s): Watanabe Mizuki、Arii Jun、Takeshima Kosuke、Fukui Ayano、Shimojima Masayuki、Kozuka-Hata Hiroko、Oyama Masaaki、Minamitani Takeharu、Yasui Teruhito、Kubota Yuji、Takekawa Mutsuhiro、Kosugi Isao、Maruzuru Yuhei、Koyanagi Naoto、Kato Akihisa、Mori Yasuko、Kawaguchi Yasushi
  • Journal Title: Journal of Virology Volume: 95 Issue: 3
  • DOI: 10.1128/jvi.01413-20
  • Peer Reviewed / Open Access
• [Journal Article] Identification of a herpes simplex virus 1 gene encoding neurovirulence factor by chemical proteomics (2020)
  • Author(s): Kato Akihisa、Adachi Shungo、Kawano Shuichi、Takeshima Kousuke、Watanabe Mizuki、Kitazume Shinobu、Sato Ryota、Kusano Hideo、Koyanagi Naoto、Maruzuru Yuhei、Arii Jun、Hatta Tomohisa、Natsume Tohru、Kawaguchi Yasushi
  • Journal Title: Nature Communications Volume: 11 Issue: 1 Pages: 4894-4894
  • DOI: 10.1038/s41467-020-18718-9
  • Peer Reviewed / Open Access
• [Journal Article] Role of Phosphatidylethanolamine Biosynthesis in Herpes Simplex Virus 1-Infected Cells in Progeny Virus Morphogenesis in the Cytoplasm and in Viral Pathogenicity In Vivo (2020)
  • Author(s): Arii Jun、Fukui Ayano、Shimanaka Yuta、Kono Nozomu、Arai Hiroyuki、Maruzuru Yuhei、Koyanagi Naoto、Kato Akihisa、Mori Yasuko、Kawaguchi Yasushi
  • Journal Title: Journal of Virology Volume: 94 Issue: 24
  • DOI: 10.1128/jvi.01572-20
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Phosphoregulation of a Conserved Herpesvirus Tegument Protein by a Virally Encoded Protein Kinase in Viral Pathogenicity and Potential Linkage between Its Evolution and Viral Phylogeny (2020)
  • Author(s): Shibazaki Misato、Kato Akihisa、Takeshima Kosuke、Ito Jumpei、Suganami Mai、Koyanagi Naoto、Maruzuru Yuhei、Sato Kei、Kawaguchi Yasushi
  • Journal Title: Journal of Virology Volume: 94 Issue: 18 Pages: 1-4
  • DOI: 10.1128/jvi.01055-20
  • Peer Reviewed / Open Access
• [Journal Article] ESCRT-III controls nuclear envelope deformation induced by progerin (2020)
  • Author(s): Arii Jun、Maeda Fumio、Maruzuru Yuhei、Koyanagi Naoto、Kato Akihisa、Mori Yasuko、Kawaguchi Yasushi
  • Journal Title: Scientific Reports Volume: 10 Issue: 1 Pages: 18877-18877
  • DOI: 10.1038/s41598-020-75852-6
  • Peer Reviewed / Open Access
• [Journal Article] Identification of the Capsid Binding Site in the Herpes Simplex Virus 1 Nuclear Egress Complex and Its Role in Viral Primary Envelopment and Replication. (2019)
  • Author(s): Takeshima K, Arii J, Maruzuru Y, Koyanagi N, Kato A, Kawaguchi Y.
  • Journal Title: J Virol. Volume: 93 Issue: 21
  • DOI: 10.1128/jvi.01290-19
  • Peer Reviewed / Open Access
• [Journal Article] A role for the CCR5?CCL5 interaction in the preferential migration of HSV-2-specific effector cells to the vaginal mucosa upon nasal immunization (2019)
  • Author(s): Joo Sunyi、Suwanto Aldina、Sato Ayuko、Nakahashi-Ouchida Rika、Mori Hiromi、Uchida Yohei、Sato Shintaro、Kurashima Yosuke、Yuki Yoshikazu、Fujihashi Kohtaro、Kawaguchi Yasushi、Kiyono Hiroshi
  • Journal Title: Mucosal Immunology Volume: 12 Issue: 6 Pages: 1391-1403
  • DOI: 10.1038/s41385-019-0203-z
  • Peer Reviewed / Open Access
• [Journal Article] Roles of the Interhexamer Contact Site for Hexagonal Lattice Formation of the Herpes Simplex Virus 1 Nuclear Egress Complex in Viral Primary Envelopment and Replication. (2019)
  • Author(s): Arii J, Takeshima K, Maruzuru Y, Koyanagi N, Kato A, Kawaguchi Y.
  • Journal Title: J Virol. Volume: 93 Issue: 14
  • DOI: 10.1128/jvi.00498-19
  • Peer Reviewed / Open Access
• [Journal Article] Combating herpesvirus encephalitis by potentiating a TLR3-mTORC2 axis. (2018)
  • Author(s): Sato R, Kato A, Chimura T, Saitoh SI, Shibata T, Murakami Y, Fukui R, Liu K, Zhang Y, Arii J, Sun-Wada GH, Wada Y, Ikenoue T, Barber GN, Manabe T, Kawaguchi Y, Miyake K.
  • Journal Title: Nat Immunol. Volume: 19 Issue: 10 Pages: 1071-1082
  • DOI: 10.1038/s41590-018-0203-2
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Roles of the Phosphorylation of Herpes Simplex Virus 1 UL51 at a Specific Site in Viral Replication and Pathogenicity. (2018)
  • Author(s): Kato A, Oda S, Watanabe M, Oyama M, Kozuka-Hata H, Koyanagi N, Maruzuru Y, Arii J, Kawaguchi Y.
  • Journal Title: J Virol. Volume: 92 Issue: 18
  • DOI: 10.1128/jvi.01035-18
  • Peer Reviewed / Open Access
• [Journal Article] Regulation of Herpes Simplex Virus 2 Protein Kinase UL13 by Phosphorylation and Its Role in Viral Pathogenesis. (2018)
  • Author(s): Koyanagi N, Kato A, Takeshima K, Maruzuru Y, Kozuka-Hata H, Oyama M, Arii J, Kawaguchi Y.
  • Journal Title: J Virol. Volume: 92 Issue: 17
  • DOI: 10.1128/jvi.00807-18
  • Peer Reviewed / Open Access
• [Journal Article] ESCRT-III mediates budding across the inner nuclear membrane and regulates its integrity. (2018)
  • Author(s): Arii J, Watanabe M, Maeda F, Tokai-Nishizumi N, Chihara T, Miura M, Maruzuru Y, Koyanagi N, Kato A, Kawaguchi Y.
  • Journal Title: Nat Commun. Volume: 9 Issue: 1 Pages: 3379-3379
  • DOI: 10.1038/s41467-018-05889-9
  • Peer Reviewed / Open Access
• [Presentation] 単純ヘルペスウイルス感染の分子機構 (2020)
  • Author(s): 川口 寧
  • Organizer: 第50回日本皮膚免疫アレルギー学会総会学術大会
  • Invited
• [Presentation] 単純ヘルペスウイルスの病原性発現機構 (2020)
  • Author(s): 川口 寧
  • Organizer: 第3回HZ・Sフォーラム
  • Invited
• [Presentation] 新規HSV-1 遺伝子の機能解析 (2019)
  • Author(s): 加藤哲久，竹島功高, 丸鶴雄平，小栁直人，有井潤，川口寧, 足達俊吾, 八田知久, 夏目徹
  • Organizer: 第33回ヘルペスウイルス研究会
• [Presentation] 単純ヘルペスウイルスによる核膜の再構築 (2019)
  • Author(s): 有井潤, 川口寧
  • Organizer: 第92回日本生化学会大会
• [Presentation] The roles of glycerophospholipids in HSV-1 replication (2019)
  • Author(s): Jun Arii, Ayano Fukui, Yuhei Maruzuru, Naoto Koyanagi, Akihisa Kato, Yasushi Kawaguchi
  • Organizer: 第67回日本ウイルス学会学術集会
• [Presentation] Novel Evasion Mechanisms against Innate and Adaptive Immune Responses by Herpes Simplex Virus (2019)
  • Author(s): Yasushi Kawaguchi
  • Organizer: 第48回日本免疫学会学術集会
  • Invited
• [Presentation] Molecular Mechanisms of Herpes Simplex Virus Replication and Pathogenicity (2019)
  • Author(s): Yasushi Kawaguchi
  • Organizer: International Joint Forum on Infectious Disease Research 2019
  • Int'l Joint Research
• [Presentation] αヘルペスウイルスの進化とUs3リン酸化部位の獲得 (2018)
  • Author(s): 柴﨑美里, 加藤哲久, 竹島功高, 丸鶴雄平, 小栁直人, 有井潤, 川口寧
  • Organizer: 第32回ヘルペスウイルス研究会
• [Presentation] 新規HSV-1遺伝子の同定 (2018)
  • Author(s): 加藤哲久, 竹島功高, 丸鶴雄平, 小栁直人, 有井潤, 川口寧, 川野秀一, 足達俊吾, 八田知久, 夏目徹
  • Organizer: 第32回ヘルペスウイルス研究会
• [Presentation] HSV type-specific phosphorylation mediated by Us3 kinase: its role in viral pathogenesis and implication in evolution of herpesviruses (2018)
  • Author(s): Misato Shibazaki, Akihisa Kato, Kosuke Takeshima, Naoto Koyanagi, Yuhei Maruzuru, Jun Arii, Yasushi Kawaguchi
  • Organizer: 第66回日本ウイルス学会学術集会
• [Presentation] A HSV-2 specific phosphorylation event mediated by Us3 kinase is involved in viral pathogenicity in mice following vaginal infection (2018)
  • Author(s): Misato Shibazaki, Akihisa Kato, Naoto Koyanagi, Yuhei Maruzuru, Jun Arii, Yasushi Kawaguchi
  • Organizer: 43rd Annual International Herpesvirus Workshop
  • Int'l Joint Research
• [Presentation] Sensing of herpes simplex virus by the host immunity and immune evasion by the virus (2018)
  • Author(s): Yasushi Kawaguchi
  • Organizer: KAI International Meeting 2018
  • Int'l Joint Research / Invited
• [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