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Research on the pathophysiology and treatment for neonate with drug-resistant herpes simplex virus infections

Research Project

Project/Area Number 15K09675
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Pediatrics
Research InstitutionNational Institute of Infectious Diseases

Principal Investigator

SAIJO MASAYUKI  国立感染症研究所, ウイルス第一部, 部長 (50300926)

Research Collaborator Fujii Hikaru  国立感染症研究所, ウイルス第一部, 流動研究員
Yamada Souichi  国立感染症研究所, ウイルス第一部, 主任研究官
Harada Shizuko  国立感染症研究所, ウイルス第一部, 主任研究官
Omura Natsumi  国立感染症研究所, ウイルス第一部, 実習生
Yoshikawa Tomoki  国立感染症研究所, ウイルス第一部, 主任研究官
Project Period (FY) 2015-04-01 – 2018-03-31
Project Status Completed (Fiscal Year 2017)
Budget Amount *help
¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000)
Fiscal Year 2017: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2016: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2015: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Keywords単純ヘルペスウイルス1型 / 新生児ヘルペス / ヘルペス脳炎 / アシクロビル / 薬剤耐性 / 神経病原性 / チミジンリン酸化酵素 / 単純ヘルペスウイルス感染症1型 / 耐性 / ウイルス性チミジンリン酸化酵素 / DNAポリメラーゼ / 単純ヘルペス脳炎 / 単純ヘルペスウイルス
Outline of Final Research Achievements

In our previous study, the amino acid substitution of H from Q at the 125th position of viral thymidine kinase (vTK) gene amplified from the central spinal fluid (CSF) of neonatal HSV-1 infection was confirmed to confer acyclovir (ACV)-resistance. In this study, recombinant HSV-1 with the mutation in vTK gene was generated artificially by using BAC system. The recombinant HSV-1 showed ACV-resistance in vitro, but maintained neurovirulence in mouse infection model. The sensitivity of ACV-resistant HSV-1 to ACV was confirmed to be associated significantly with the neurovirulence in mouse infection model, being that the higher the resistance, lower the neurovirulence in mice. The present study indicates that virological test of and selection of proper treatment for the patients, who showed intractable HSV-1 disease against ACV-therapy, are required,

Report

(4 results)
  • 2017 Annual Research Report   Final Research Report ( PDF )
  • 2016 Research-status Report
  • 2015 Research-status Report
  • Research Products

    (16 results)

All 2018 2017 2016 2015

All Journal Article (5 results) (of which Peer Reviewed: 5 results,  Open Access: 1 results,  Acknowledgement Compliant: 2 results) Presentation (11 results) (of which Int'l Joint Research: 3 results,  Invited: 1 results)

  • [Journal Article] Application of next-generation sequencing to detect acyclovir-resistant herpes simplex virus type 1 variants at low frequency in thymidine kinase gene of the isolates recovered from patients with hematopoietic stem cell transplantation2018

    • Author(s)
      Fujii Hikaru、Kakiuchi Satsuki、Tsuji Masanori、Nishimura Hidekazu、Yoshikawa Tomoki、Yamada Souichi、Omura Natsumi、Inagaki Takuya、Shibamura Miho、Harada Shizuko、Taniguchi Shuichi、Saijo Masayuki
    • Journal Title

      Journal of Virological Methods

      Volume: 251 Pages: 123-128

    • DOI

      10.1016/j.jviromet.2017.10.019

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Acyclovir sensitivity and neurovirulence of herpes simplex virus type 1 with amino acid substitutions in the viral thymidine kinase gene, which were detected in the patients with intractable herpes simplex encephalitis previously reported.2018

    • Author(s)
      5.Inagaki T, Satoh M, Fujii H, Yamada S, Shibamura M, Yoshikawa T, Harada S, Takeyama H, Saijo M.
    • Journal Title

      Jpn J Infect Dis

      Volume: 印刷中

    • NAID

      130007485614

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Acyclovir-resistant herpes simplex virus type 1 infection after HLA-haploidentical stem cell transplantation2017

    • Author(s)
      三上 真充、平家 俊男、足立 壯一、梅田 雄嗣、松田 浩一、才田 聡、平松 英文、藤野 寿典、山田 壮一、柴村 美帆、西條 政幸
    • Journal Title

      The Japanese Journal of Pediatric Hematology / Oncology

      Volume: 54 Issue: 5 Pages: 408-411

    • DOI

      10.11412/jspho.54.408

    • NAID

      130006707510

    • ISSN
      2187-011X, 2189-5384
    • Related Report
      2017 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Association between sensitivity of viral thymidine kinase-associated acyclovir-resistant herpes simplex viru type 1 and virulence.2017

    • Author(s)
      Omura N, Fujii H, Yoshikawa T, Yamada S, Harada S, Inagaki T, Shibamura M, Takeyama H, Saijo M.
    • Journal Title

      Virology Journal

      Volume: 14 Issue: 1 Pages: 59-59

    • DOI

      10.1186/s12985-017-0728-2

    • Related Report
      2016 Research-status Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] The association of the emergence of acyclovir-resistant herpes simplex vrus type 1 with the prognosis in hematopoietic stem cell transplantation patients.2017

    • Author(s)
      Kakiuchi S, Tsuji M, Nishimura H, Yoshikawa T, Wang L, Takayama-Ito M, Kinoshita H, Lim CK, Fujii H, Yamada S, Harada S, Oka A, Mizuguchi M, Taniguchi S, Saijo M.
    • Journal Title

      Journal of Infectious Diseases

      Volume: 215 Issue: 6 Pages: 865-873

    • DOI

      10.1093/infdis/jix042

    • Related Report
      2016 Research-status Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Presentation] Application of next-generation sequencing to detect acyclovir resistant herpes simplex virus 1 variants at low frequency in thymidine kinase gene from viral isolates, emergence in patients with stem cell transplantations2017

    • Author(s)
      Fujii H, Kakiuchi S, Yoshikawa T, Yamada S, Omura N, Shibamura M, Harada S, Saijo M.
    • Organizer
      17th International Congress of Virology
    • Related Report
      2017 Annual Research Report
    • Int'l Joint Research
  • [Presentation] DNAポリメラーゼ変異によるアシクロビル耐性HSV-1を特異的に誘導するためのシステム開発2017

    • Author(s)
      原田志津子,藤井ひかる,吉河智城,大村夏美,稲垣拓也,柴村美帆,加藤博史,山田壮一,西條政幸
    • Organizer
      第27回坑ウイルス療法学会学術集会・総会
    • Related Report
      2017 Annual Research Report
  • [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型の遺伝子変異の経時的な解析2017

    • Author(s)
      藤井ひかる、垣内五月、大村夏美、柴村美帆、吉河智城、山田壮一、原田志津子、西條政幸
    • Organizer
      第27回坑ウイルス療法学会学術集会・総会
    • Related Report
      2017 Annual Research Report
  • [Presentation] Characterization of alphaherpesvirus isolated from fruits bats in Vietnam2017

    • Author(s)
      稲垣拓哉,山田壮一,藤井ひかる,吉河智城,原田志津子,長谷部太,竹山春子,西條政幸
    • Organizer
      第65回日本ウイルス学会学術集会
    • Related Report
      2017 Annual Research Report
  • [Presentation] DNAポリメラーゼ変異によるアシクロビル耐性HSV-1を特異的に誘導するためのシステム開発2017

    • Author(s)
      藤井ひかる,原田志津子,吉河智城,大村夏美,稲垣拓也,柴村美帆,加藤博史,山田壮一,西條政幸
    • Organizer
      第65回日本ウイルス学会学術集会
    • Related Report
      2017 Annual Research Report
  • [Presentation] Analysis of acyclovir resistant herpes simplex virus 1 variants, emergence in patients with stem cell transplantation2016

    • Author(s)
      Hikaru Fujii, Satsuki Kakiuchi, Natsumi Omura, Miho Shibamura, Tomoki Yoshikawa, Souichi Yamada, Sizuko Harada, Masayuki Saijo
    • Organizer
      第64回日本ウイルス学会学術集会
    • Place of Presentation
      札幌市
    • Year and Date
      2016-10-23
    • Related Report
      2016 Research-status Report
  • [Presentation] Establishment of the recombinant vaccinia virus, LC16m8, that expresses severe fever with thrombocytopenia syndrome virus glycoprotein as a potential SFTS vaccine2016

    • Author(s)
      Natsumi Omura, Tomoki Yoshikawa, Hideki Tani, Shuetsu Fukushi, Satoshi Taniguchi, Miho Shibamura, Hikaru Fujii, Shizuko Harada, Masanobu Kimura, Soichi Yamada, Masayuki Shimojima, Shigeru Morikawa, Masayuki Saijo
    • Organizer
      XXI International Poxvirus, Asfarvirus, and Iridovirus Conference
    • Place of Presentation
      Strasbourg, France
    • Year and Date
      2016-07-02
    • Related Report
      2016 Research-status Report
    • Int'l Joint Research
  • [Presentation] Recovery of infectious vaccinia virus from a bacterial artificial chromosome, which retains the full-length viral genomic DNA of a third generation smallpox vaccine strain, LC16m82016

    • Author(s)
      Miho Shibamura, Tomoki Yoshikawa, Hikaru Fujii, Natsumi Omura, Shizuko Harada, Soichi Yamada, Masayuki Saijo
    • Organizer
      XXI International Poxvirus, Asfarvirus, and Iridovirus Conference
    • Place of Presentation
      Strasbourg, France
    • Year and Date
      2016-07-02
    • Related Report
      2016 Research-status Report
    • Int'l Joint Research
  • [Presentation] 単純ヘルペス脳炎の診断におけるアシクロビル耐性株の検出2016

    • Author(s)
      西條政幸
    • Organizer
      第57回日本神経学会
    • Place of Presentation
      福岡市
    • Year and Date
      2016-05-18
    • Related Report
      2016 Research-status Report
    • Invited
  • [Presentation] Virulence of the Thymidine Kinase-Associated Acyclovir-Resistant Herpes Simplex Virus Type 12015

    • Author(s)
      大村夏美,藤井ひかる,吉川智城,山田壮一,原田志津子,竹山春子,西條政幸
    • Organizer
      第63回日本ウイルス学会学術集会
    • Place of Presentation
      福岡
    • Year and Date
      2015-11-22
    • Related Report
      2015 Research-status Report
  • [Presentation] チミジンキナーゼ変異関連アシクロビル耐性単純ヘルペスウイルス1型の病原性解析2015

    • Author(s)
      大村夏美,藤井ひかる,吉川智城,山田壮一,原田志津子,竹山春子,西條政幸
    • Organizer
      第25回日本抗ウイルス療法学会総会
    • Place of Presentation
      東京
    • Year and Date
      2015-05-22
    • Related Report
      2015 Research-status Report

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Published: 2015-04-16   Modified: 2019-03-29  

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