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Control of intractable herpes simplex virus infections in immunocompromised children in Japan

Research Project

Project/Area Number 18K07894
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Review Section Basic Section 52050:Embryonic medicine and pediatrics-related
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)

Project Period (FY) 2018-04-01 – 2021-03-31
Project Status Completed (Fiscal Year 2020)
Budget Amount *help
¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000)
Fiscal Year 2020: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2019: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2018: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Keywords単純ヘルペスウイルス1型 / 水痘帯状疱疹ウイルス / 抗ウイルス薬 / アシクロビル / 耐性 / 薬剤感受性 / Bウイルス / 中枢神経感染症 / 単純ヘルペスウイルス1型 / Bウイルス感染症 / 脳炎 / 遺伝子検査法 / 単純ヘルペスウイルス / 薬剤耐性 / 免疫不全 / 薬剤感受性試験 / 免疫不全患者
Outline of Final Research Achievements

The specimens collected from patients with intractable herpes simplex virus infections, varicella zoster virus infections, and cytomegalovirus infections were tested for sensitivity to antiviral agents. New mechanism of action for ACV-resistance that a mutation in the UL29 gene confers ACV-resistance was elucidated for the first time. HSV-1, which has a stop codon at the 44th position between the first and the second methionine, showed ACV-resistance, because the expression level of the viral thymidine kinase was reduced in a temperature dependent manner.
Two patients with neurological symptoms were retrospectively diagnosed as having B virus infections by detection of B virus-specific genome in the cerebrospinal fluid. These cases are the patients diagnosed with B virus infection for the first time in Asia as well as in Japan.

Academic Significance and Societal Importance of the Research Achievements

免疫不全患者における薬剤耐性ヘルペスウイルス感染症の診断と治療の重要性はあまり認識されていない.国内で難治性ヘルペスウイルス感染症に関するウイルス学的な検査を実施できる施設は極めて限られている.これは造血幹細胞移植患者を含む免疫不全患者におけるヘルペスウイルス感染症への適切な診断と治療を難しくしている.本研究を通じて薬剤耐性ヘルペスウイルス感染症患者が少なからず存在することが再確認された.ヘルペスウイルス薬剤感受性試験を実施できる体制を構築する必要がある.
これまで欧米(特に米国)でのみ確認されていたサル由来Bウイルスによる脳炎患者が日本でも確認された.検査法および治療法開発が必要である.

Report

(4 results)
  • 2020 Annual Research Report   Final Research Report ( PDF )
  • 2019 Research-status Report
  • 2018 Research-status Report
  • Research Products

    (17 results)

All 2020 2019 2018

All Journal Article (9 results) (of which Peer Reviewed: 7 results,  Open Access: 3 results) Presentation (8 results) (of which Invited: 1 results)

  • [Journal Article] New Mechanism of Acyclovir Resistance in Herpes Simplex Virus 1, Which Has a UAG Stop Codon between the First and Second AUG Initiation Codons2020

    • Author(s)
      Nguyen PHA, Yamada S, Shibamura M, Inagaki T, Fujii H, Harada S, Fukushi S, Mizuguchi M, Saijo M
    • Journal Title

      Japanese Journal of Infectious Diseases

      Volume: 73 Issue: 6 Pages: 447-451

    • DOI

      10.7883/yoken.JJID.2020.313

    • NAID

      130007942254

    • ISSN
      1344-6304, 1884-2836
    • Year and Date
      2020-11-30
    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Characterization of a Novel Alphaherpesvirus Isolated from the Fruit Bat Pteropus lylei in Vietnam2020

    • Author(s)
      Inagaki T, Yamada S, Fujii H, Yoshikawa T, Shibamura M, Harada S, Fukushi S, Le MQ, Nguyen CT, Nguyen TTT, Nguyen TT, Nguyen TT, Quach VT, Thong VD, Mori K, Sasaki M, Setiyono A, Handharyani E, Takeyama H, Hasebe F, Saijo M
    • Journal Title

      Journal of Virology

      Volume: 94 Issue: 18

    • DOI

      10.1128/jvi.00673-20

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed
  • [Journal Article] 一人の免疫不全患者から学ぶウイルス感染症学: 薬剤耐性単純ヘルペスウイルス1型感染症2020

    • Author(s)
      西條 政幸
    • Journal Title

      神経感染症

      Volume: 25 Pages: 1-6

    • NAID

      130007841896

    • Related Report
      2020 Annual Research Report 2019 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] 免疫不全患者における薬剤耐性単純ヘルペスウイルス感染症と対策.2019

    • Author(s)
      西條政幸
    • Journal Title

      Precision Medicine

      Volume: 2 Pages: 872-878

    • Related Report
      2019 Research-status Report
  • [Journal Article] Differences in the Likelihood of Acyclovir Resistance-Associated Mutations in the Thymidine Kinase Genes of Herpes Simplex Virus 1 and Varicella-Zoster Virus2019

    • Author(s)
      Fujii Hikaru、Harada Shizuko、Yoshikawa Tomoki、Yamada Souichi、Omura Natsumi、Shibamura Miho、Inagaki Takuya、Kato Hirofumi、Fukushi Shuetsu、Saijo Masayuki
    • Journal Title

      Antimicrobial Agents and Chemotherapy

      Volume: 63 Issue: 5

    • DOI

      10.1128/aac.00017-19

    • Related Report
      2019 Research-status Report 2018 Research-status Report
    • Peer Reviewed / Open Access
  • [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 Reported2018

    • Author(s)
      Inagaki Takuya、Satoh Masaaki、Fujii Hikaru、Yamada Souichi、Shibamura Miho、Yoshikawa Tomoki、Harada Shizuko、Takeyama Haruko、Saijo Masayuki
    • Journal Title

      Japanese Journal of Infectious Diseases

      Volume: 71 Issue: 5 Pages: 343-349

    • DOI

      10.7883/yoken.JJID.2018.176

    • NAID

      130007485614

    • ISSN
      1344-6304, 1884-2836
    • Year and Date
      2018-09-30
    • Related Report
      2018 Research-status Report
    • Peer Reviewed
  • [Journal Article] Severe acyclovir-resistant herpes simplex virus 1 infection following cord blood transplantation2018

    • Author(s)
      Shigemura Tomonari、Nakazawa Yozo、Yoshikawa Tomoki、Fujii Hikaru、Yamada Souichi、Saijo Masayuki、Okuyama Ryuhei
    • Journal Title

      International Journal of Hematology

      Volume: 108 Issue: 3 Pages: 237-238

    • DOI

      10.1007/s12185-018-2480-9

    • Related Report
      2018 Research-status Report
    • Peer Reviewed
  • [Journal Article] A Novel System for Constructing a Recombinant Highly-Attenuated Vaccinia Virus Strain (LC16m8) Expressing Foreign Genes and Its Application for the Generation of LC16m8-Based Vaccines against Herpes Simplex Virus 22018

    • Author(s)
      Omura Natsumi、Yoshikawa Tomoki、Fujii Hikaru、Shibamura Miho、Inagaki Takuya、Kato Hirofumi、Egawa Kazutaka、Harada Shizuko、Yamada Souichi、Takeyama Haruko、Saijo Masayuki
    • Journal Title

      Japanese Journal of Infectious Diseases

      Volume: 71 Issue: 3 Pages: 229-233

    • DOI

      10.7883/yoken.JJID.2017.458

    • NAID

      130006743930

    • ISSN
      1344-6304, 1884-2836
    • Related Report
      2018 Research-status Report
    • Peer Reviewed
  • [Journal Article] 造血幹細胞移植患者におけるアシクロビル耐性ヘルペスウイルス.2018

    • Author(s)
      柴村美帆,権藤久司,西條政幸.
    • Journal Title

      血液内科

      Volume: 76 Pages: 675-681

    • NAID

      40021578108

    • Related Report
      2018 Research-status Report
  • [Presentation] 一人の免疫不全患者から学ぶウイルス感染症学.2019

    • Author(s)
      西條政幸.
    • Organizer
      第24回日本神経感染症学会
    • Related Report
      2019 Research-status Report
    • Invited
  • [Presentation] 過去30年の日本人女性におけるCMV(サイトメガロウイルス)中和抗体保有率の変遷.2019

    • Author(s)
      柴村美帆,西條政幸.
    • Organizer
      第60回日本臨床ウイルス学会
    • Related Report
      2019 Research-status Report
  • [Presentation] チミジンリン酸化酵素(TK)遺伝子を欠損させ,VZVのTK遺伝子を挿入させたキメラウイルスHSV-1-VZV-TKの特殊なアシクロビル耐性化機序の解析.2019

    • Author(s)
      山田壮一,藤井ひかる,原田志津子,吉河智城、稲垣拓哉,柴村美帆,福士秀悦,西條政幸.
    • Organizer
      第29回抗ウイルス療法学会
    • Related Report
      2019 Research-status Report
  • [Presentation] 国立感染症研究所ウイルス第一部が引き受けているヘルペスウイルス薬剤感受性試験の受付状況,方法.その知見.2019

    • Author(s)
      山田壮一,福士秀悦,津田美穂子,福井良子,柴村美帆,原田志津子,西條政幸.
    • Organizer
      第29回抗ウイルス療法学会
    • Related Report
      2019 Research-status Report
  • [Presentation] A mutation in HSV-1 UL29 gene confers HSV-1 acyclovir-resistance.2019

    • Author(s)
      Souichi Yamada, Shizuko Harada, Hikaru Fujii, Tomoki Yoshikawa, Takuya Inagaki, Miho Sibamura, Shuetsu Fukushi, Masayuki Saijo.
    • Organizer
      第67回日本ウイルス学会
    • Related Report
      2019 Research-status Report
  • [Presentation] 単純ヘルペスウイルス1型および水痘・帯状疱疹ウイルスのチミジンキナーゼ遺伝子上におけるアシクロビル耐性責任変異の出現パターンの比較.2018

    • Author(s)
      Harada S, Fujii H, Yoshikawa T, Yamada S, Omura N, Inagaki T, Shibamura M, Kato H, Saijo M.
    • Organizer
      第66回日本ウイルス学会
    • Related Report
      2018 Research-status Report
  • [Presentation] 報告されているアシクロビル治療抵抗性HSV-1脳炎患者で検出されたHSV-1チミジンキナーゼ遺伝子変異のアシクロビル耐性誘導能.2018

    • Author(s)
      稲垣拓哉,藤井ひかる,佐藤正明,山田壮一,吉河智城,柴村美帆,原田志津子,竹山晴子,西條政幸.
    • Organizer
      第23回日本神経感染症学会
    • Related Report
      2018 Research-status Report
  • [Presentation] Analysis of a novel acyclovir-resistance mechanism of a chimeric HSV-1 deleted with its thymidine kinase (TK) gene but inserted with VZV-TK gene.2018

    • Author(s)
      Yamada S, Fujii H, Harada S, Yoshikawa T, Omura N, Inagaki T, hibamura M, Kato H, Saijo M.
    • Organizer
      第66回日本ウイルス学会
    • Related Report
      2018 Research-status Report

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Published: 2018-04-23   Modified: 2022-01-27  

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