Study on the therapeutic strategy for acyclovir-resistant HSV-1 infections in neonate

• Project/Area Number: 24591591
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Pediatrics
• Research Institution: National Institute of Infectious Diseases
• Principal Investigator: SAIJO MASAYUKI 国立感染症研究所, その他部局等, その他 (50300926)
• Project Period (FY): 2012-04-01 – 2015-03-31
• Project Status: Completed (Fiscal Year 2014)
• Budget Amount: ¥5,070,000 (Direct Cost: ¥3,900,000、Indirect Cost: ¥1,170,000); Fiscal Year 2014: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000); Fiscal Year 2013: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2012: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
• Keywords: 新生児ヘルペス / ヘルペス脳炎 / 薬剤耐性 / 単純ヘルペスウイルス1型 / アシクロビル / ウイルス性チミジンリン酸化酵素 / 造血幹細胞移植 / 免疫不全

Outline of Final Research Achievements

The neonatal herpes with encephalitis, which was resistance to acyclovir (ACV) therapy, was virologically confirmed to be caused by ACV-resistant herpes simplex virus type 1 (HSV-1) in this study for the first time. DNA polymerase-associated ACV-resistant HSV-1 was generated by selection of the HSV-1 with S2242. Most of the viruses were sensitive or hypersensitive to ganciclovir, while they were cross-resistant to foscarnet. In recent years, the number of patients with immunodeficiency including those who received organ transplantation, suggesting that drug-resistant HSV-1 infections might become a great concern. The diagnostic system including the sensitivity assay and effective therapeutic strategies should be prepared in advance.

Research Products

• [Journal Article] アシクロビル耐性単純ヘルペスウイルスによる脳炎の診断と治療戦略 (2014)
  • Author(s): 西條政幸
  • Journal Title: 臨床神経学 Volume: 54 Pages: 1024-1027
  • Open Access
• [Journal Article] Characterization of DNA Polymerase-Associated Acyclovir-Resistant Herpes Simplex Virus Type 1: Mutations, Sensitivity to Antiviral Compounds, Neurovirulence, and In-Vivo Sensitivity to Treatment (2013)
  • Author(s): Wang LX, Takayama-Ito M, Kinoshita-Yamaguchi H, Kakiuchi S, Suzutani T, Nakamichi K, Lim CK, Kurane I, Saijo M.
  • Journal Title: Japanese Journal of Infectious Diseases Volume: 66 Issue: 5 Pages: 404-410
  • DOI: 10.7883/yoken.66.404
  • NAID: 130003381717
  • ISSN: 1344-6304, 1884-2836
  • Peer Reviewed
• [Journal Article] Detection of human herpesviruses in the cerebrospinal fluid from patients diagnosed with or suspected of having progressive multifocal leukoencephalopathy (2013)
  • Author(s): K. Nakamichi, N. Inoue, T. Shimokawa, I. Kurane, C.K. Lim, M. Saijo
  • Journal Title: BMC Neurology Volume: 13(200) Issue: 1 Pages: 200-200
  • DOI: 10.1186/1471-2377-13-200
  • Peer Reviewed
• [Journal Article] Neonatal herpes encephalitis caused by a virologically confirmed acyclovir resistant herpes simplex virus type 1 (2013)
  • Author(s): Kakiuchi S, Nonoyama S, Wakamatsu H, Kogawa K, Wang L, Kinoshita-Yamaguchi H, Takayama-Ito M, Lim CK, Inoue N, Mizuguchi M, Igarashi T, Saijo M
  • Journal Title: J. Clin. Microbiol Volume: 51 Issue: 1 Pages: 356-9
  • DOI: 10.1128/jcm.02247-12
  • Peer Reviewed
• [Presentation] Association of acyclovir-resistant herpes simplex virus 1 emergence with their outcome in hematopoietic stem cell transplantation patients. (2014)
  • Author(s): Satsuki Kakiuchi, Masanori Tsuji, Hidekazu Nishimura, Mutsuyo Ito-Takayama, Chang-Kweng Lim, Madoka Horiya, Yukie Yamaguchi, Shuichi Taniguchi, Masashi Mizuguchi, Akira Oka, Masayuki Saijo.
  • Organizer: International Union of Microbiological Societies Congress
  • Place of Presentation: Montreal, Canada
  • Year and Date: 2014-07-27 – 2014-08-01
• [Presentation] Acyclovir-resistant herpes simplex virus 1 shedding and the mortality in the hematopoietic stem cell transplantation patients. (2014)
  • Author(s): Masayuki Saijo, Satsuki Kakiuchi, Masanori Tsuji, Hidekazu Nishimura, Mutsuyo Ito-Takayama, Madoka Horiya, Yukie Yamaguchi, Shuichi Taniguchi, Masashi Mizuguchi, Akira Oka, Chang-Kweng Lim.
  • Organizer: 39th Annual International Herpesvirus Workshop
  • Place of Presentation: Kobe city, Japan
  • Year and Date: 2014-07-19 – 2014-07-23
• [Presentation] アシクロビル耐性単純ヘルペスウイルスによる脳炎の診断と治療戦略． (2014)
  • Author(s): 西條政幸
  • Organizer: 第55回日本神経学会学術大会
  • Place of Presentation: 福岡
  • Year and Date: 2014-05-21 – 2014-05-24
  • Invited
• [Presentation] アシクロビル耐性ヘルペスウイルス脳炎症例報告から同定された単純ヘルペスウイルス1型のチミジンキナーゼ41番目アミノ酸変異はアシクロビル耐性を誘導しない． (2013)
  • Author(s): 佐藤正明，垣内五月，木下（山口）一美，伊藤（高山）睦代，林昌宏，西條政幸．
  • Organizer: 第23回抗ウイルス療法研究会総会
  • Place of Presentation: 東京
• [Presentation] 造血幹細胞移植患者におけるアシクロビル耐性単純ヘルペスウイルス1型についての検討． (2013)
  • Author(s): 垣内五月，王麗欣，伊藤睦代，林昌宏，辻正徳，谷口修一，西村秀一，岡明，水口雅，西條政幸．
  • Organizer: 第23回抗ウイルス療法研究会総会
  • Place of Presentation: 東京
• [Presentation] ヘルペス脳炎を起因した単純ヘルペスウイルス1型のアシクロビル感受性の検討． (2013)
  • Author(s): 垣内五月，佐藤正明，伊藤(高山)睦代，林昌宏，蒲ひかり，東裕哉，大澤由記子，木村聡，津川潤，坪井義夫，水口雅，岡明，西條政幸．
  • Organizer: 日本小児感染症学会
  • Place of Presentation: 札幌
• [Presentation] 造血幹細胞移植におけるアシクロビル耐性単純ヘルペスウイルス1型感染症の臨床的意義に関する研究． (2013)
  • Author(s): 垣内五月，王麗欣，伊藤睦代，林昌宏，辻正徳，谷口修一，西村秀一，岡明，水口雅，西條政幸．
  • Organizer: 第61回日本ウイルス学会学術集会
  • Place of Presentation: 神戸
• [Presentation] ウイルス分離が不可能なヘルペス脳炎病原ウイルスの薬剤感受性試験法の開発と臨床応用． (2013)
  • Author(s): 佐藤正明、垣内五月、木下（山口）一美、伊藤（高山）睦代、林昌宏、西條政幸．
  • Organizer: 第61回日本ウイルス学会学術集会
  • Place of Presentation: 神戸
• [Presentation] Drug-resistant herpes simplex virus type 1 infections in children (2012)
  • Author(s): Masayuki Saijo, Satsuki Kakiuchi
  • Organizer: The 9th Japan-China International Conference of Virology
  • Place of Presentation: Sapporo
• [Presentation] 神経ウイルス感染症の遺伝子診断とその応用 (2012)
  • Author(s): 西條政幸
  • Organizer: 第17回日本神経感染症学会総会・学術集会
  • Place of Presentation: 京都
• [Remarks] 感染研年報（H24年度）ウイルス第一部
  • URL: http://www.nih.go.jp/niid/images/annual/h24/201201.pdf