Analyses of herpesvirus-infected cells by real time imaging

• Project/Area Number: 20390130
• 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, 准教授 (60292984)
• Co-Investigator(Kenkyū-buntansha): UEMA Masashi 東京大学, 医科学研究所, 特任研究員 (70456193) ; 福田 誠 東京大学, 医科学研究所, 特任研究員 (10447336)
• Project Period (FY): 2008 – 2010
• Project Status: Completed (Fiscal Year 2010)
• Budget Amount: ¥19,630,000 (Direct Cost: ¥15,100,000、Indirect Cost: ¥4,530,000); Fiscal Year 2010: ¥5,720,000 (Direct Cost: ¥4,400,000、Indirect Cost: ¥1,320,000); Fiscal Year 2009: ¥6,630,000 (Direct Cost: ¥5,100,000、Indirect Cost: ¥1,530,000); Fiscal Year 2008: ¥7,280,000 (Direct Cost: ¥5,600,000、Indirect Cost: ¥1,680,000)
• Keywords: HSV / リアルタイムイメージング / ウイルス粒子成熟

Research Abstract

Using the real-time imaging system, we identified the site of HSV-1 final envelopment as trans-Golgi network. Moreover, we identified a binding partner of UL12, which is involved in nuclear egress pathway, as nucleolin and showed that nucleolin was required for efficient nuclear egress of HSV-1 capsids.

Research Products

• [Journal Article] Anterograde transport of herpes simplex virus capsids in neurons by Senarate and Married mechanisms. (2011)
  • Author(s): T.W.Wisner, et al.
  • Journal Title: Journal of Virology Volume: (In Press)(掲載確定)
  • Peer Reviewed
• [Journal Article] Non-muscle myosin IIA is a functional entry receptor for herpes simplex virus 1. (2010)
  • Author(s): J.Arii, H.Goto, T.Suenaga, M.Oyama, H.Kozuka-Hata, T.Imai, A.Minowa, H.Akashi, H.Arase, Y.Kawaoka, Y.Kawaguchi.
  • Journal Title: Nature 467 Pages: 859-862
• [Journal Article] A Single Amino Acid Substitution in Herpes simplex virus 1 Envelope Glycoprotein B at a Site Required for Binding to the Paired Immunoglobulin-like Type 2 Receptor a (PILRτ) Abrogates PILRτ-dependent Viral Entry and Reduces Pathogenesis. (2010)
  • Author(s): J.Arii, J.Wang, T.Morimoto, T.Suenaga, H.Akashi, H.Arase, Y.Kawaguchi.
  • Journal Title: J.Virol. 84 Pages: 10773-10783
• [Journal Article] Nucleolin is required for efficient nuclear egress of herpes simplex virus 1 nucleocapsids. (2010)
  • Author(s): K.Sagou, M.Uema, Y.Kawaguchi.
  • Journal Title: J.Virol. 84 Pages: 2110-2121
• [Journal Article] Effects of Phosphorylation of Herpes Simplex Virus 1 Envelope Glycoprotein B by Us3 Kinase In Vivo and In Vitro. (2010)
  • Author(s): T.Imai, K.Sagou, J.Arii, Y.Kawaguchi.
  • Journal Title: J.Virol. 84 Pages: 153-162
• [Journal Article] Selective control of type I IFN induction by the Rac activator DOCK2 during TLR!Vmediated plasmacytoid dendritic cell activation. (2010)
  • Author(s): K.Gotoh, Y.Tanaka, A.Nishikimi, R.Nakamura, H.Yamada, N.Maeda, T.Ishikawa, K.Hoshino, T.Uruno, Q.Cao, S.Higashi, Y.Kawaguchi, M.Enjoji, R.Takayanagi, T.Kaisho, Y.Yoshikai, Y.Fukui.
  • Journal Title: J.Exp.Med. 207 Pages: 721-730
• [Journal Article] Myelin-associated glycoprotein mediates membrane fusion and entry of neurotropic herpesviruses. (2010)
  • Author(s): T.Suenaga, T.Satoh, P.Somboonthum, Y.Kawaguchi, Y.Mori, H.Arase
  • Journal Title: Proc.Natl.Acad.Sci.USA 107 Pages: 866-871
• [Journal Article] Characterization of a thymidine kinase-deficient mutant of equine herpesvirus 4 and in vitro susceptibility of the virus to antiviral agents. (2010)
  • Author(s): W.Azab, K.Tsujimura, K.Kato, J.Arii, T.Morimoto, Y.Kawaguchi, Y.Tohya, T.Matsumura, H.Akashi.
  • Journal Title: Antiviral Res. 85 Pages: 389-395
• [Journal Article] Nucleolin is required for efficient nuclear egress of herpes simplex virus 1 nucleocansids. (2010)
  • Author(s): K.Sagou, et al.
  • Journal Title: Journal of Virology Volume: 84 Pages: 2110-2121
  • Peer Reviewed
• [Journal Article] Non-muscle myosin ILA is a functional entry receptor for herpes simplex virus 1. (2010)
  • Author(s): J. Arii, et al.
  • Journal Title: Nature Volume: 467 Pages: 859-862
  • Peer Reviewed
• [Journal Article] Binding of herpes simplex virus glycoprotein B (gB) to PILR￡\ depends on specific sialylated O-linked glycans on gB. (2009)
  • Author(s): J.Wang, F.Fan, T.Satoh, J.Arii, L.L.Lanier, P.G.Spear, Y.Kawaguchi, H.Arase.
  • Journal Title: J.Virol. 83 Pages: 13042-13045
• [Journal Article] Differences in the Regulatory and Functional Effects of the Us3 Protein Kinase Activities of Herpes Simplex Virus 1 and 2. (2009)
  • Author(s): T.Morimoto, J.Arii, M.Tanaka, T.Sata, H.Akashi, M.Yamada, Y.Nishiyama, M.Uema, Y.Kawaguchi.
  • Journal Title: J.Virol. 83 Pages: 11624-11634
• [Journal Article] Herpesvirus protein ICP27 switches PML isoform by altering mRNA splicing. (2009)
  • Author(s): T.Nojima, T.Oshiro-Ideue, H.Nakanoya, H.Kawamura, T.Morimoto, Y.Kawaguchi, N.Kataoka,, M.Hagiwara.
  • Journal Title: Nucleic Acids Res. 37 Pages: 6515-6527
• [Journal Article] Analysis of herpesvirus host specificity determinants using herpesvirus genomes as bacterial artificial chromosomes. (2009)
  • Author(s): J.Arii, K.Kato, Y.Kawaguchi, Y.Tohya, H.Akashi.
  • Journal Title: Microbiol.Immunol. 53 Pages: 433-441
  • NAID: 10027687107
• [Journal Article] TRAF6 establishes innate immune responses by activating NF-kB and IRF7 upon sensing cytosolic viral RNA and DNA. (2009)
  • Author(s): H.Konno, T.Yamamoto, K.Yamazaki, J.Gohda, T.Akiyama, K.Semba, H.Goto, A.Kato, T.Yujiri, T.Imai, Y.Kawaguchi, B.Su, O.Takeuchi, S.Akira, Y.Tsunetsugu-Yokota, J.Inoue.
  • Journal Title: PLoS ONE 4
• [Journal Article] Epstein-Barr virus protein kinase BGLF4 interacts with viral transactivator BZLF1 and regulates its transactivation activity. (2009)
  • Author(s): R.Asai, A.Kato, Y.Kawaguchi.
  • Journal Title: J.Gen.Virol. 90 Pages: 1575-1581
• [Journal Article] Regulation of the Catalytic Activity of Herpes Simplex Virus 1 Protein Kinase Us3 by Auto-Phosphorylation and Its Role in Pathogenesis. (2009)
  • Author(s): K.Sagou, T.Imai, H.Sagara, M.Uema, Y.Kawaguchi.
  • Journal Title: J.Virol. 83 Pages: 5773-5783
• [Journal Article] Entry of herpes simplex virus 1 and other alphaherpesviruses via the paired immunoglobulin-like type 2 receptorハτ. (2009)
  • Author(s): J.Arii, M.Uema, T.Morimoto, H.Sagara, H.Akashi, E.Ono, H.Arase, Y.Kawaguchi.
  • Journal Title: J.Virol. 83 Pages: 4520-4527
• [Journal Article] Herpesvirus gB-induced fusion between the virion envelope and outer nuclear membrane during virus egress is regulated by the viral US3 kinase. (2009)
  • Author(s): T.W.Wisner, C.C.Wright, A.Kato, Y.Kawaguchi, F.Mou, J.D.Baines, R.J.Roller, D.C.Johnson.
  • Journal Title: J.Virol. 83 Pages: 3115-3126
• [Journal Article] Identification of multiple sites in herpes simplex virus genomes suitable for insertion of foreign genes. (2009)
  • Author(s): T.Morimoto, J.Arii, H.Akashi, Y.Kawaguchi.
  • Journal Title: Microbiol.Immunol. 53 Pages: 155-161
• [Journal Article] Herpes simplex virus 1 protein kinase Us3 phosphorylates viral envelope glycoprotein B and regulates its expression on the cell surface. (2009)
  • Author(s): A.Kato, J.Arii, I.Shiratori, H.Akashi, H.Arase, Y.Kawaguchi.
  • Journal Title: J.Virol. 83 Pages: 250-261
• [Journal Article] Entry of herpes simplex virus 1 and other alphaherpesviruses via the paired immunoglobulin-like type 2 receptor α. (2009)
  • Author(s): J.Arii, et al.
  • Journal Title: Journal of Virology Volume: 83 Pages: 4520-4527
  • Peer Reviewed
• [Journal Article] Identification of multiple sites in herpes simplex virus genomes suit able for insertion of foreign genes. (2009)
  • Author(s): T.Morimoto, et al.
  • Journal Title: Microbiology and Immunology Volume: 53 Pages: 155-161
  • Peer Reviewed
• [Journal Article] Herpesvirus gB-induced fusion between the virion envelope and outer nuclear membrane during virus egress is regulated by the viral US3 kinase. (2009)
  • Author(s): T.W.Wisner, et al.
  • Journal Title: Journal of Virology Volume: 83 Pages: 3115-3126
  • Peer Reviewed
• [Journal Article] Identification of a physiological phosphorylation site of the Herpes simplex virus 1-encoded protein kinase Us3 which regulates its optimal catalytic activity in vitro and influences its function in infected cells. (2008)
  • Author(s): A.Kato, M.Tanaka, M.Yamamoto, R.Asai, T.Sata, Y.Nishiyama, Y.Kawaguchi.
  • Journal Title: J.Virol. 82 Pages: 6172-6189
• [Journal Article] Simultaneous tracking of capsid, tegument, and envelop protein localization in living cells infected with thriple fluorescent herpes simplex virus 1. (2008)
  • Author(s): K.Sugimoto, M.Uema, H.Sagara, M.Tanaka, T.Sata, Y.Hashimoto, Y.Kawaguchi.
  • Journal Title: J.Virol. 82 Pages: 5198-5211
• [Journal Article] PILRa is a herpes simplex-1 entry co-receptor that associates with glycoprotein B. (2008)
  • Author(s): T.Satoh, J.Arii, T.Suemaga, J.Wang, A.Kogure, J.Uehori, N.Arase, I.Shiratori, S.Tanaka, T.Satoh, J.Arii, T.Suemaga, J.Wang, A.Kogure, J.Uehori, N.Arase, I.Shiratori, S.Tanaka, Y.Kawaguchi, P.G.Spear, L.L.Lanier, H.Arase.
  • Journal Title: Cell 132 Pages: 1-10
• [Journal Article] Microarray analysis of transcriptional responses to infection by herpes simplex virus types 1 and 2 and their US3-deficient mutants. (2008)
  • Author(s): Kamakura, M., Nawa, A., Ushijima, Y., Goshima, F., Kawaguchi, Y., Kikkawa, F., Nishiyama, Y.
  • Journal Title: Microbes and Infection 10 Pages: 405-413
• [Journal Article] Evaluation of therapeutic effects of antiviral agents using a silkworm baculovirus infection model. (2008)
  • Author(s): Y.Orihara, H.Hamamoto, H.Kasuga, T.Shimada, Y.Kawaguchi, K.Shekimizu.
  • Journal Title: J.Gen.Virol. 89 Pages: 188-194
• [Journal Article] Primary target cells of herpes simplex virus type 1 in the hippocampus. (2008)
  • Author(s): Y.Ando, H.Kitamura, Y.Kawaguchi, Y.Koyanagi.
  • Journal Title: Microbes and Infection 10 Pages: 1514-1523
• [Journal Article] The Product of UL7 gene of Herpes simplex virus type 1 interacts with a Mitochondria protein, Adenine nucleotide translocator 2. (2008)
  • Author(s): M.Tanaka, T.Sata, Y.Kawaguchi.
  • Journal Title: Virology J. 5 Pages: 125-137
• [Journal Article] Simultaneous tracking of capsid, tegument, and envelop protein localization in living cells infected with triple fluorescent herpes simplex virus 1 (2008)
  • Author(s): K.Sugimoto, et al.
  • Journal Title: J.Virol 82 Pages: 5198-5211
  • Peer Reviewed
• [Journal Article] Identification of a physiological phosphorylation site of the Herpes simplex virus 1-encoded protein kinase Us3 which regulates its optimal catalytic activity in vitro and influences its function in infected cells (2008)
  • Author(s): A.Kato, et al.
  • Journal Title: J.Virol. 82 Pages: 1514-1523
  • Peer Reviewed
• [Journal Article] Role of the Herpes Simplex Virus 1 Us3 Kinase Phosphorylation Site and Endocytosis Motifs in EnvelopeGlycoprotein B in Its Intracellular Transport and Neurovirulence.
  • Author(s): T.Imai, J.Arii, A.Minowa, A.Kakimoto, N.Koyanagi, A.Kato, Y.Kawaguchi.
  • Journal Title: J.Virol. in press
• [Journal Article] Anterograde transport of herpes simplex virus capsids in neurons by Separate and Married mechanisms.
  • Author(s): T.W.Wisner, K.Sugimoto, P.Howard, Y.Kawaguchi, D.C.Johnson.
  • Journal Title: J.Virol. in press
• [Presentation] ヘルペスウイルスの新規受容体の同定 (2010)
  • Author(s): 川口寧
  • Organizer: 平成22年度筆界同大学遺伝子病制御研究所共同研究集会「感染・炎症・発癌」
  • Place of Presentation: 札幌(招待講演)
• [Presentation] Non-muscle myosin IIA is a functional entry receptor for herpes simplex virus 1. (2010)
  • Author(s): 川口寧
  • Organizer: The 7th China-Japan Joint Laboratory Workshop-Pathogenesis, Gene Regulation and Signal Transduction
  • Place of Presentation: Beijing, China.
• [Presentation] Role of Us3 phosphorylation on HSV-1 gB in its endocytosis and pathogenesis. (2010)
  • Author(s): T.Imai, J.Arii, A.Kato, K.Sagou, Y.Kawaguchi
  • Organizer: 35^<th> International Herpesvirus Workshop
  • Place of Presentation: Salt Lake City, USA.
• [Presentation] たった1アミノ酸のリン酸化によるウイルス病態発現の分子機構 (2010)
  • Author(s): 川口寧
  • Organizer: 第10回日本蛋白質科学会年会
  • Place of Presentation: 札幌(招待講演)
• [Presentation] Regulatory and functional effects of protein kinases encoded by herpesviruses on host cells. (2010)
  • Author(s): 川口寧
  • Organizer: Seminar in Reprogramming of host cells by microbial effectors in Institut fur Klinische und Molekulare Virologie Universitat Erlangen-Nurnberg Erlangen
  • Place of Presentation: Germany(招待講演)
• [Presentation] ウイルスプロテインキナーゼの機能と病態への関与 (2010)
  • Author(s): 川口寧
  • Organizer: 平成22年度筆界同大学遺伝子病制御研究所共同研究集会「感染・炎症・発癌」
  • Place of Presentation: 札幌(招待講演)
• [Presentation] Regulation and functions of HSV Us3 protein kinases. (2010)
  • Author(s): 川口寧
  • Organizer: 14^<th> International Conference on Immunology and Prophylaxis of Human Herpesvirus Infections.
  • Place of Presentation: Kobe, Japan(招待講演)
• [Presentation] Roles of Us3 phosphorylation on HSV-1 gB in its endocytosis and patho genesis (2010)
  • Author(s): T.Imai, et al.
  • Organizer: 35^<th> International Herpesvirus Workshop
  • Place of Presentation: Salt Lake City, USA
• [Presentation] Regulation of the catalytic activity of HSV protein kinase Us3 and its role in pathogenesis. (2009)
  • Author(s): K.Sagou, T.Morimoto, J.Arii, T.Imai, M.Tanaka, Y.Nishiyama, M.Uema, Y.Kawaguchi
  • Organizer: 34^<th> International Herpesvirus Workshop Ithaca
  • Place of Presentation: USA.
• [Presentation] Entry of herpes simplex virus 1 and other aplhaherpesviruses via the paired immunoglobulin-like type 2 receptor . (2009)
  • Author(s): J.Arii, J.Wang, M.Uema, T.Morimoto, H.Sagara, H.Akashi, E.Ono, H.Arase, Y.Kawaguchi
  • Organizer: 34^<th> International Herpesvirus Workshop Ithaca
  • Place of Presentation: USA.
• [Presentation] Regulation of the catalytic activity of HSVUs3 protein kinases in infected cells. (2009)
  • Author(s): 川口寧
  • Organizer: A Scientific Symposium for Dr.Bernard Roizman: Honoring six decades of scientific research, teaching and service.
  • Place of Presentation: Chicago, USA.
• [Presentation] リアルタイムイメージングによるウイルス粒子成熟過程の解析-ヌクレオカプシドの核膜通過機構と宿主細胞因子のウイルス粒子への取り込み機構 (2009)
  • Author(s): 川口寧, 等
  • Organizer: 第57回日本ウイルス学会
  • Place of Presentation: 都市センターホテル(東京)
• [Presentation] Molecular mechanisms of viral replication and pathogenesis unveiled by fluores cent herpes simplex viruses (2008)
  • Author(s): Y.Kawaguchi
  • Organizer: The 8^<th> Awaji International Forum on Infection and Immunity
  • Place of Presentation: Awaji-shima
  • Year and Date: 2008-09-09
• [Presentation] Molecular mechanisms of viral replication and pathogenesis unveiled by fluorescent herpes simplex viruses. (2008)
  • Author(s): 川口寧
  • Organizer: 8^<th> Awaji International Forum on Infection and Immunity.
  • Place of Presentation: Awaji, Japan(招待講演)
• [Presentation] Herpesvirus vectors-How to generate the vectors.Educational Semminar (2008)
  • Author(s): 川口寧
  • Organizer: 第14回日本遺伝子治療学会
  • Place of Presentation: 札幌(招待講演)
• [Presentation] ヘルペスウイルス生活環の可視化.そのインパクトと臨床応用 シンポジウム (Bench to Bed side) (2008)
  • Author(s): 川口寧
  • Organizer: 第49回日本臨床ウイルス学会
  • Place of Presentation: 犬山(招待講演)
• [Remarks] ホームページ等
  • URL: http://www.ims.u-tokyo.ac.jp/Kawaguchi-lab/KawaguchiLabTop.html
• [Remarks]
  • URL: http://www.ims.u-tokyo.ac.jp/Kawaguchi-lab/KawaguchiLabTop.html
• [Remarks]
  • URL: http://www.ims.u-tokyo.ac.jp/Kawaguchi-lab/KawaguchiLabTop.html
• [Remarks]
  • URL: http://www.ims.u-tokyo.ac.jp/Kawaguchi-lab/KawaguchiLabTop.html
• [Patent(Industrial Property Rights)] 組換えウイルス、これを保持する大腸菌およびその製造法 (2008)
  • Inventor(s): 川口寧、森本智美
  • Industrial Property Rights Holder: 国立大学法人東京大学
  • Industrial Property Number: 2008-142662
  • Filing Date: 2008-05-30
• [Patent(Industrial Property Rights)] 組換えイルス、これを保持する大腸菌およびその製造法 (2008)
  • Inventor(s): 川口寧, 等
  • Industrial Property Rights Holder: 東京大学
  • Industrial Property Number: 2008-142662
  • Filing Date: 2008-05-30