Molecular basis of replication and pathogenesis of herpes simplex virus

2010 Fiscal Year Final Research Report

• Project Area: Matrix of Infection Phenomena
• Project/Area Number: 18073007
• Research Category: Grant-in-Aid for Scientific Research on Priority Areas
• Allocation Type: Single-year Grants
• Review Section: Biological Sciences
• Research Institution: Nagoya University
• Principal Investigator: NISHIYAMA Yukihiro Nagoya University, 医学系研究科, 教授 (60115615)
• Project Period (FY): 2006 – 2010
• Keywords: 単純ヘルペスウイルス / DNAウイルス / ウイルス遺伝子機能 / ウイルス病原性 / ウイルス増殖機構

Research Abstract

The purpose of this study is to understand the molecular mechanism of the replication and pathogenesis of an important human pathogen, herpes simplex virus (HSV). The present studies have revealed the novel functions and roles of HSV gene products. Moreover, cellular proteins, INSM1 and tankylase 1 have been shown to play important roles in the replication of HSV. These observations were useful for developing vaccines and oncolytic viruses.

Research Products

• [Journal Article] Mitochondria and viruses. (2011)
  • Author(s): Ohta A, Nishiyama Y.
  • Journal Title: Mitochondrion. 11(1) Pages: 1-12
  • Peer Reviewed
• [Journal Article] Apoptosis induction after herpes simplex virus infection differs according to cell type in vivo. (2010)
  • Author(s): Esaki, S., Goshima, F., Katsumi, S., Watanabe, D., Ozaki, N., Murakami, S., Nishiyama, Y.
  • Journal Title: Archieves of Virology 155 Pages: 1235-1245
  • Peer Reviewed
• [Journal Article] Carrier cell-based delivery of replication- competent HSV-1 mutants enhances antitumor effect for ovarian cancer. (2010)
  • Author(s): Fujiwara, S., Nawa, A., Luo, CH., Kamakura, M., Goshima, F., Kondo, C., Kiyono, T., Kikkawa, F., Nishiyama, Y.
  • Journal Title: Cancer Gene Therapy 18 Pages: 77-86
  • Peer Reviewed
• [Journal Article] Herpes simplex virus UL56 interacts with and regulates the Nedd4-family ubiquitin ligase Itch. (2010)
  • Author(s): Ushijima Y, Luo C, Kamakura M, Goshima F, Kimura H, Nishiyama Y.
  • Journal Title: Virology Journal. 7(1) Pages: 179
  • 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 Pathogens 7 Pages: e1000530
  • Peer Reviewed
• [Journal Article] Herpes simplex viruuuumplex virux viruex viru viru viruegument protein UL56 relocalizes ubiquitin ligase Nedd4 and has a role in transport and/or release of virions. (2009)
  • Author(s): Ushijima, Y., Goshima, F., Kimura, H., Nishiyama, Y.
  • Journal Title: Virology Journal 6 Pages: 168
  • Peer Reviewed
• [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): Morimoto, T., Arii, J., Tanaka, M., Sata, T., Akashi, H., Yamada, M., Nishiyama, Y., Uema, M., Kawaguchi, Y.
  • Journal Title: Journal of Virology 83 Pages: 11624-11634
  • Peer Reviewed
• [Journal Article] Protective role of Fas-FasL signaling in lethal infection with herpes simplex virus type 2 in mice. (2009)
  • Author(s): Ishikawa, T., Yamada, H., Oyamada, A., Goshima, F., Nishiyama, Y., Yoshikai, Y.
  • Journal Title: Journal of Virology 83 Pages: 11777-11783
  • Peer Reviewed
• [Journal Article] A regulatory role of interleukin 15 in wound healing and mucosal infection in mice. (2008)
  • Author(s): Kagimoto, Y., Yamada, H., Ishikawa, T., Maeda, N., Goshima, F., Nishiyama, Y., Furue, M., Yoshikai, Y.
  • Journal Title: Journal of Leukocyte Biology 83 Pages: 165-172
  • Peer Reviewed
• [Journal Article] The UL14 Tegument Protein of Herpes Simplex Virus Type 1 (HSV-1) is Required for Efficient Nuclear Transport of the Alpha Transinducing Factor VP16 and Viral Capsids. (2008)
  • Author(s): Yamauchi Y, Kiriyama K, Kubota N, Kimura H, Usukura J, Nishiyama Y.
  • Journal Title: Journal of Virology 82 Pages: 1094-1106
  • Peer Reviewed
• [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
  • Peer Reviewed
• [Journal Article] Herpes Simplex Virus Type 2 UL56 Interacts with the Ubiquitin Ligase Nedd4 and Increases its Ubiquitination. (2008)
  • Author(s): Ushijima Y, Koshizuka T, Goshima F, Kimura H, Nishiyama Y.
  • Journal Title: Journal of Virology 82 Pages: 5220-5233
  • Peer Reviewed
• [Journal Article] Herpes Simplex Virus Induces Extensive Modification and Dynamic Relocalisation of the Nuclear Mitotic Apparatus Protein (NuMA) in Interphase Cells (2008)
  • Author(s): Yamauchi, Y., Kiriyama, K., Kimura, H., Nishiyama, Y.
  • Journal Title: Journal of Cell Science 121 Pages: 2087-2096
  • 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): Kato, A., Tanaka, M., Yamamoto, M., Asai, R., Sata, T., Nishiyama, Y., Kawaguchi, Y.
  • Journal Title: Journal of Virology 82 Pages: 6172-6189
  • Peer Reviewed
• [Journal Article] Non-engineered, naturally oncolytic herpes simplex virus HSV1 HF-10 : applications for cancer gene therapy. (2008)
  • Author(s): Nawa A, Luo C, Zhang L, Ushjima Y, Ishida D, Kamakura M, Fujimoto Y, Goshima F, Kikkawa F, Nishiyama Y.
  • Journal Title: Curr Gene Therapy 8 Pages: 208-221
  • Peer Reviewed
• [Journal Article] Intercellular trafficking and cytotoxicity of recombinant HSV-1 thymidine kinase fused with HSV-2 US11 RXP repeat peptide. (2007)
  • Author(s): Luo, C., Nawa, A., Yamauchi, Y., Kohno, S., Ushijima, Y., Goshima, F., Nishiyama, Y.
  • Journal Title: Virus Genes 34 Pages: 263-272
  • Peer Reviewed
• [Journal Article] Determination and analysis of the DNA sequence of highly attenuated herpes simplex virus type 1 mutant HF10, a potential oncolytic virus. (2007)
  • Author(s): Ushijima Y, Luo C, Goshima F, Yamauchi Y, Kimura H, Nishiyama Y.
  • Journal Title: Microbes and Infection 9(2) Pages: 142-149
  • Peer Reviewed
• [Journal Article] Suitability of a US3-inactivated HSV mutant(L1BR1) as an oncolytic-virus for pancreatic cancer therpay. (2007)
  • Author(s): Kasuya, H., Nishiyama, Y., Nomoto, S., Goshima, F., Takeda, S., Watanabe, I., Nomura, N., Shikano, T., Fujii, T., Kanazumi, N., Nakao, A.
  • Journal Title: Cancer Gene Therapy 14 Pages: 533-542
  • Peer Reviewed
• [Journal Article] Oncolytic Virotherapy with an HSV amplicon vector expressing granulocyte-macrophage colony-stimulating factor using the replication-competent HSV type I mutant HF10 as a helper (2007)
  • Author(s): Kohno, S., Luo, C., Nawa, A., Fujimoto, Y., Waranabe, D., Goshima, F., Tsurumi, T., Nishiyama, Y.
  • Journal Title: Cancer Gene Therapy 14 Pages: 918-926
  • Peer Reviewed
• [Journal Article] Herpes simplex virus protein UL11 but not UL51 is associated with lipid rafts. (2007)
  • Author(s): Koshizuka, T., Kawaguchi, Y., Nozawa, N., Mori, I., Nishiyama, Y.
  • Journal Title: Virus Genes 35 Pages: 571-575
  • Peer Reviewed
• [Journal Article] Replication-competent, oncolytic herpes simplex virus type 1 mutants induce a bystander effect following ganciclovir treatment. (2007)
  • Author(s): Luo, C., Mori, I., Goshima, F., Ushijima, Y., Nawa, A., Kimura, H., Nishiyama, Y.
  • Journal Title: Journal of Gene Medicine 9 Pages: 875-883
  • Peer Reviewed
• [Journal Article] Herpes simplex virus US3 protein kinase regulates virus-induced apoptosis in olfactory and vomeronasal chemosensory neurons in vivo. (2006)
  • Author(s): Mori, I., Goshima, F., Watanabe, D., Ito, H., Koide, N., Yoshida, T., Liu, B., Kimura, Y., Yokochi, T., Nishiyama, Y.
  • Journal Title: Microbes and infection 8 Pages: 1806-1812
  • Peer Reviewed
• [Journal Article] Herpes simplex virus 1-encoded protein kinase UL13 phosphorylates the viral US3 protein kinase and regulates nuclear localization of viral envelopment factors UL34 and UL31. (2006)
  • Author(s): Kato, A., Yamamoto, M., Ohno, T., Tanaka, M., Sata, T., Nishiyama,Y., Kawaguchi, Y.
  • Journal Title: Journal of Virology 80 Pages: 1476-1486
  • Peer Reviewed
• [Journal Article] Association of two membrane proteins encoded by herpes simplex virus type2, UL11 and UL56. (2006)
  • Author(s): Koshizuka, T., Kawaguchi, Y., Goshima, F., Mori, I., Nishiyama, Y.
  • Journal Title: Virus Genes 32 Pages: 153-163
  • Peer Reviewed
• [Journal Article] Accessory genes define the relationship between the herpes simplex virus and its host. (2006)
  • Author(s): Mori, I., Nishiyama, Y.
  • Journal Title: Microbes and Infection 8 Pages: 2556-2562
  • Peer Reviewed
• [Journal Article] Replication-competent herpes simplex virus : a novel and promising modality for cancer therapy. (2006)
  • Author(s): Mori, I., Nishiyama, Y.
  • Journal Title: Current Topics in Virology 5 Pages: 21-30
  • Peer Reviewed
• [Presentation] 単純ヘルペス1型感染後期におけるUL14の遺伝子産物の役割 (2009)
  • Author(s): 太田茜、山内洋平、武藤義文、西山幸廣
  • Organizer: 第57回日本ウイルス学会学術集会
  • Place of Presentation: 東京
  • Year and Date: 2009-10-25
• [Presentation] HSV-2感染によるNedd4ファミリーユビキチンリガーゼの変化とUL56遺伝子産物の役割 (2009)
  • Author(s): 牛島洋子、駱晨虹、鎌倉真紀、五島典、西山幸廣
  • Organizer: 第57回日本ウイルス学会学術集会
  • Place of Presentation: 東京
  • Year and Date: 2009-10-25