Analysis of VZV latency induced by antigenic modulation

• Project/Area Number: 25293108
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Partial Multi-year Fund
• Section: 一般
• Research Field: Virology
• Research Institution: University of Toyama
• Principal Investigator: Shiraki Kimiyasu 富山大学, 大学院医学薬学研究部(医学), 教授 (50135745)
• Co-Investigator(Renkei-kenkyūsha): DAIKOKU Tohru 北陸大学, 薬学部, 教授 (80291409) ; TAKEMOTO Masaya 北陸大学, 薬学部, 講師 (60379237) ; YAJIMA Misako 東北医科薬科大学, 医学部, 助教 (60443131)
• Research Collaborator: KUROSA Yoshikazu ; ASANO Yoshizo ; SUZUKI Yasuhiko ; OHNO Ayumu
• Project Period (FY): 2013-04-01 – 2018-03-31
• Project Status: Completed (Fiscal Year 2017)
• Budget Amount: ¥17,160,000 (Direct Cost: ¥13,200,000、Indirect Cost: ¥3,960,000); Fiscal Year 2017: ¥3,380,000 (Direct Cost: ¥2,600,000、Indirect Cost: ¥780,000); Fiscal Year 2016: ¥3,380,000 (Direct Cost: ¥2,600,000、Indirect Cost: ¥780,000); Fiscal Year 2015: ¥3,380,000 (Direct Cost: ¥2,600,000、Indirect Cost: ¥780,000); Fiscal Year 2014: ¥3,380,000 (Direct Cost: ¥2,600,000、Indirect Cost: ¥780,000); Fiscal Year 2013: ¥3,640,000 (Direct Cost: ¥2,800,000、Indirect Cost: ¥840,000)
• Keywords: 水痘帯状疱疹ウイルス / 抗原変調 / 潜伏感染 / 中和抗体 / ウイルス感染性 / ウィルス / 転写因子 / クロマチン / 抗原偏重作用 / 帯状疱疹

Outline of Final Research Achievements

Treatment with neutralizing antibody against varicella-zoster virus of infected cell induced antigenic modulation leading to latent state similar to the latency in neurons. Colocalization of the immediate early proteins and the transcription factor SP1 in untrated infected cells was altered by the antigenic modulation. Buthionine sulfoximine (BSO) treatment slowed the disappearance of their colocalization from the nucleus and prevented latent infection. Furthermore, Viral DNA become chromatin-associated status in latent infection, but BSO increased the amounts of chromainted free viral DNA.

Research Products

• [Journal Article] Age-dependent trigeminal and female-specific lumbosacral increase in herpes zoster distribution in the elderly (2018)
  • Author(s): Shiraki Kimiyasu、Toyama Nozomu、Shiraki Atsuko、Yajima Misako
  • Journal Title: J Dermatol Sci. Volume: in press Issue: 2 Pages: 166-171
  • DOI: 10.1016/j.jdermsci.2018.01.009
  • Peer Reviewed
• [Journal Article] Helicase-primase inhibitor amenamevir for herpesvirus infection: Towards practical application for treating herpes zoster (2017)
  • Author(s): Shiraki K.
  • Journal Title: Drugs Today Volume: 53 Issue: 11 Pages: 573-573
  • DOI: 10.1358/dot.2017.53.11.2724803
  • Peer Reviewed
• [Journal Article] Characterization of susceptibility variants of poliovirus grown in the presence of favipiravir (2017)
  • Author(s): Tohru Daikoku, Mineyuki Mizuguchi, Takayuki Obita, Takeshi Yokoyama, Yoshihiro Yoshida, Masaya Takemoto, Kimiyasu Shiraki
  • Journal Title: Journal of Microbiology, Immunology and Infection Volume: 印刷中 Issue: 5 Pages: 30100-7
  • DOI: 10.1016/j.jmii.2017.03.004
  • Peer Reviewed / Open Access
• [Journal Article] Interaction of immunoglobulin with cytomegalovirus-infected cells. (2017)
  • Author(s): Nobuyasu Aiba, Atsuko Shiraki, Misako Yajima, Yukari Oyama, Yoshihiro Yoshida, Ayumu Ohno, Hiroshi Yamada, Masaya Takemoto, Tohru Daikoku, Kimiyasu Shiraki
  • Journal Title: Viral Immunology Volume: 印刷中 Issue: 7 Pages: 500-507
  • DOI: 10.1089/vim.2016.0151
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Herpes Zoster and Recurrent Herpes Zoster (2017)
  • Author(s): Shiraki Kimiyasu、Toyama Nozomu、Daikoku Tohru、Yajima Misako、for the Miyazaki Dermatologist Society
  • Journal Title: Open Forum Infect Dis Volume: 4 Issue: 1 Pages: 007-007
  • DOI: 10.1093/ofid/ofx007
  • Peer Reviewed / Open Access
• [Journal Article] Acyclovir-resistant herpes simplex virus 1 infection early after allogeneic hematopoietic stem cell transplantation with T-cell depletion (2017)
  • Author(s): Akahoshi Yu、Kanda Junya、Ohno Ayumu、Komiya Yusuke、Gomyo Ayumi、Hayakawa Jin、Harada Naonori、Kameda Kazuaki、Ugai Tomotaka、Wada Hidenori、Ishihara Yuko、Kawamura Koji、Sakamoto Kana、Sato Miki、Terasako-Saito Kiriko、Kimura Shun-ichi、Kikuchi Misato、Nakasone Hideki、Kako Shinichi、Shiraki Kimiyasu、Kanda Yoshinobu
  • Journal Title: J Infect Chemother. Volume: 23 Issue: 7 Pages: 485-487
  • DOI: 10.1016/j.jiac.2017.02.001
  • Peer Reviewed
• [Journal Article] T-705 (Favipiravir) suppresses tumor necrosis factor α production in response to influenza virus infection: A beneficial feature of T-705 as an anti-influenza drug (2017)
  • Author(s): T. TANAKA, T. KAMIYAMA, T. DAIKOKU, K. TAKAHASHI, N. NOMURA, M. KUROKAWA, K. SHIRAKI
  • Journal Title: Acta Virologica Volume: 61 Issue: 01 Pages: 48-55
  • DOI: 10.4149/av_2017_01_48
  • Peer Reviewed
• [Journal Article] Profile of anti-herpetic action of ASP2151 (amenamevir) as a helicase-primase inhibitor (2017)
  • Author(s): Yajima Misako、Yamada Hiroshi、Takemoto Masaya、Daikoku Tohru、Yoshida Yoshihiro、Long Tan、Okuda Tomoko、Shiraki Kimiyasu
  • Journal Title: Antiviral Res Volume: 139 Pages: 95-101
  • DOI: 10.1016/j.antiviral.2016.12.008
  • Peer Reviewed
• [Journal Article] Characterization of susceptibility variants of poliovirus grown in the presence of favipiravir (2017)
  • Author(s): Tohru Daikoku, Mineyuki Mizuguchi, Takayuki Obita, Takeshi Yokoyama, Yoshihiro Yoshida, Masaya Takemoto, and Kimiyasu Shiraki
  • Journal Title: Journal of Microbiology, Immunology and Infection Volume: 印刷中
  • Int'l Joint Research
• [Journal Article] Novel deletion in glycoprotein G forms a cluster and causes epidemiologic spread of herpes simplex virus type 2 infection. (2013)
  • Author(s): Daikoku T, Horiba K, Kawana T, Hirano M, Shiraki K.
  • Journal Title: Journal of Medical Virology Volume: 85 (10) Issue: 10 Pages: 1818-1828
  • DOI: 10.1002/jmv.23668
  • Peer Reviewed
• [Journal Article] Rapid detection of human cytomegalovirus UL97 and UL54 mutations for antiviral resistance in clinical specimens (2013)
  • Author(s): Tohoru Daikoku, Kazuhide Saito, Takamitsu Aihara, Masahiro Ikeda, Yoshiyuki Takahashi, Hiroki Hosoi, Tetsuya Nishida, Masaya Takemoto,Kimiyasu Shiraki.
  • Journal Title: Microbiol Immunol Volume: 57 Issue: 5 Pages: 396-399
  • DOI: 10.1111/1348-0421.12043
  • Peer Reviewed
• [Journal Article] Synergistic activity of amenamevir (ASP2151) with nucleoside analogs against herpes simplex virus types 1 and 2 and varicella-zoster virus (2013)
  • Author(s): Chono K, Katsumata K, Suzuki H, Shiraki K.
  • Journal Title: Antiviral Research Volume: 97 (2) Issue: 2 Pages: 154-160
  • DOI: 10.1016/j.antiviral.2012.12.006
  • Peer Reviewed
• [Journal Article] Favipiravir (T-705), a novel viral RNA polymerase inhibitor. (2013)
  • Author(s): Furuta Y, Gowen BB, Takahashi K, Shiraki K, Smee DF, Barnard DL.
  • Journal Title: Antiviral Research Volume: 100 (2) Issue: 2 Pages: 446-454
  • DOI: 10.1016/j.antiviral.2013.09.015
  • Peer Reviewed
• [Presentation] Neutralizing antibody against VZV gH modulates localization of IE62, IE63, and Sp1 during termination of productive infection. (2014)
  • Author(s): Takemoto M, Daikoku T, Yajima M, Asano Y, Shiraki K.
  • Organizer: The 39th Annual International Herpesvirus Workshop (IHW)
  • Place of Presentation: Koube
  • Year and Date: 2014-07-19 – 2014-07-23
• [Presentation] 免疫グロブリン製剤のVZVとCMV中和抗体価の比較 (2014)
  • Author(s): 白木公康
  • Organizer: 第36回日本造血細胞移植学会総会
  • Place of Presentation: 宜野湾
• [Presentation] Identification of ribonucleotide reductase mutation causing temperature-sensitivity of herpes simplex virus isolates from recurrent witlow by genome wide sequence. (2013)
  • Author(s): Shiraki K
  • Organizer: 38th Annual International Herpesvirus Workshop
  • Place of Presentation: Grand Rapids, Michigan, USA
• [Presentation] Identification of Ribonucleotide Reductase Mutation Causing Temperature-Sensitivity of Herpes Simplex Virus Isolates from Recurrent Whitlow by Genome Wide Sequence. (2013)
  • Author(s): Daikoku T, Oyama Y, Sekizuka T, Kuroda M, Sata T, Shiraki K
  • Organizer: 38th Annual International Herpesvirus Workshop
  • Place of Presentation: Grand Rapids, Michigan, USA
• [Presentation] 帯状疱疹疫学と帯状疱疹の2回発症 (2013)
  • Author(s): 白木公康
  • Organizer: 第87回日本感染症学会学術講演会第61回日本化学療法学会総会合同学会
  • Place of Presentation: 横浜
• [Presentation] 細菌性トリプシン様プロテアーゼによるインフルエンザウイルスの活性化とT-705及びオセルタミビルの作用 (2013)
  • Author(s): 白木公康，田中知暁，野村伸彦
  • Organizer: 第87回日本感染症学会学術講演会第61回日本化学療法学会総会合同学会
  • Place of Presentation: 横浜
• [Presentation] インフルエンザウイルス感染によって誘導されるサイトカイン産生に及ぼすT-705の作用 (2013)
  • Author(s): 田中知暁，野村伸彦，白木公康
  • Organizer: 第87回日本感染症学会学術講演会第61回日本化学療法学会総会合同学会
  • Place of Presentation: 横浜
• [Presentation] 細菌性トリプシン様プロテアーゼとノイラミニダーゼによるインフルエンザウイルスの活性化とT-705及びオセルタミビルの作用 (2013)
  • Author(s): 白木公康，大黒 徹
  • Organizer: 第54回日本臨床ウイルス学会
  • Place of Presentation: 倉敷
• [Presentation] 単純ヘルペス・帯状疱疹治療の新しい可能性 (2013)
  • Author(s): 白木公康
  • Organizer: 第77回日本皮膚科学会東部支部学術大会
  • Place of Presentation: さいたま
  • Invited
• [Presentation] 単純ヘルペスウイルス臨床分離株の次世代シークエンサーによる変異部位の網羅的解析 (2013)
  • Author(s): 大黒 徹，雄山由香利，矢島美彩子，関塚剛史，黒田 誠，佐多徹太郎，武本眞清，白木公康
  • Organizer: 第61回日本ウイルス学会学術集会
  • Place of Presentation: 神戸
• [Presentation] 水痘帯状疱疹ウイルスの抗gH中和抗体による潜伏感染誘導時の転写制御 (2013)
  • Author(s): 武本眞清，大黒 徹，白木公康
  • Organizer: 第61回日本ウイルス学会学術集会
  • Place of Presentation: 神戸
• [Presentation] ヘルペスウイルス感染症 (2013)
  • Author(s): 白木公康
  • Organizer: 日本性感染症学会第26回学術大会
  • Place of Presentation: 岐阜
• [Presentation] 性器ヘルペス患者から分離された単純ヘルペスウイルス2型におけるTKの変異および薬剤耐性 (2013)
  • Author(s): 丹内秀典，尾上泰彦，尾上智彦，松尾光馬，本田まり子，白木公康
  • Organizer: 日本性感染症学会第26回学術大会
  • Place of Presentation: 岐阜
• [Presentation] 単純ヘルペスウイルス臨床分離株の次世代シークエンサーによる変異部位の網羅的解析 (2013)
  • Author(s): 雄山由香利，白木公康
  • Organizer: 日本性感染症学会第26回学術大会
  • Place of Presentation: 岐阜
• [Presentation] 1369例の帯状疱疹の臨床診断とPCR法による診断について
  • Author(s): 白木公康，外山 望，宮崎県皮膚科医会
  • Organizer: 第136回日本皮膚科学会宮崎地方会
  • Place of Presentation: 宮崎