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Development of ultra-sensitive PCR testing technology for a wide range of neuroinfections including progressive multifocal leukoencephalopathy

Research Project

Project/Area Number 17K09768
Research Category

Grant-in-Aid for Scientific Research (C)

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

Principal Investigator

Kazuo Nakamichi  国立感染症研究所, ウイルス第一部, 主任研究官 (50348190)

Project Period (FY) 2017-04-01 – 2021-03-31
Project Status Completed (Fiscal Year 2020)
Budget Amount *help
¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000)
Fiscal Year 2019: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2018: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Fiscal Year 2017: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Keywordsウイルス / 中枢神経系 / 感染症 / 臨床検査 / 脱髄疾患 / 脳 / 神経感染症 / 神経脱髄疾患 / ポリオーマウイルス / 進行性多巣性白質脳症 / JCウイルス / 検査技術 / 脳神経疾患 / 検査 / ウィルス / 医療・福祉
Outline of Final Research Achievements

Progressive Multifocal Leukoencephalopathy (PML) is a fatal demyelinating disease that occurs mainly in patients with impaired T-cell immunity and is caused by the infection of JC virus (JCV) in the white matter of the brain. A PCR examination targeting genomic DNA of JCV in cerebrospinal fluid is effective in the diagnosis of PML. In this study, we developed an ultra-sensitive PCR test system that dramatically improved the detection sensitivity by concentrating JCV particles in the specimen. In addition, by applying multiplex PCR targeting neurological viruses other than JCV to this system, we demonstrated the usefulness of the ultra-sensitive PCR test for other neurological infections.

Academic Significance and Societal Importance of the Research Achievements

脳脊髄液中の病原ウイルスを標的とした一般的なPCR検査の検出下限値は約200コピー/mLである。対して、本研究で開発および実用化した超高感度PCR検査は、検体中のウイルス粒子を濃縮することで10コピー/mLまでの標的を捕捉することができる。従来の検査と比較して約20倍の検出感度を有する超高感度検査を用いることで、これまでは検出しえなかった患者の体内におけるJCVおよび他の神経系ウイルスの動態の解析が可能となった。加えて、本研究では、臨床情報と紐付けられた多数の臨床検体を用いて検査系の信頼性を確認している。以上の成果は、神経感染症の病態機序の解明ならびにそれらの早期診断において意義を有する。

Report

(5 results)
  • 2020 Annual Research Report   Final Research Report ( PDF )
  • 2019 Research-status Report
  • 2018 Research-status Report
  • 2017 Research-status Report
  • Research Products

    (37 results)

All 2021 2020 2019 2018 2017

All Journal Article (14 results) (of which Peer Reviewed: 14 results,  Open Access: 10 results) Presentation (23 results) (of which Int'l Joint Research: 2 results,  Invited: 3 results)

  • [Journal Article] Characterization of JC Polyomavirus Derived from COS-IMRb Cells2021

    • Author(s)
      Nukuzuma Souichi、Nukuzuma Chiyoko、Kameoka Masanori、Sugiura Shigeki、Nakamichi Kazuo、Tasaki Takafumi、Hidaka Koushi、Takegami Tsutomu
    • Journal Title

      Japanese Journal of Infectious Diseases

      Volume: 74 Issue: 1 Pages: 48-53

    • DOI

      10.7883/yoken.JJID.2020.325

    • NAID

      130007973723

    • ISSN
      1344-6304, 1884-2836
    • Year and Date
      2021-01-29
    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Progressive multifocal leukoencephalopathy in a patient with primary amyloid light-chain amyloidosis2020

    • Author(s)
      Katsuse Kazuto、Akiyama Kaho、Ishida Tadao、Kitayama Chigusa、Ishibashi Yoshitaka、Ochi Mieko、Kumasaka Toshio、Takahashi Kenta、Suzuki Tadaki、Nakamichi Kazuo、Saijo Masayuki、Hashida Hideji
    • Journal Title

      Clinical Neurology and Neurosurgery

      Volume: 192 Pages: 105709-105709

    • DOI

      10.1016/j.clineuro.2020.105709

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Pomalidomide-associated progressive multifocal leukoencephalopathy in multiple myeloma: cortical susceptibility-weighted imaging hypointense findings prior to clinical deterioration2020

    • Author(s)
      Ueno Hiroki、Kikumto Mai、Takebayashi Yoshiko、Ishibashi Haruka、Takahashi Tetsuya、Yasutomi Hiroko、Umemoto Kasane、Nakamichi Kazuo、Saijo Masayuki、Ichinohe Tatsuo、Maruyama Hirofumi
    • Journal Title

      Journal of NeuroVirology

      Volume: 26 Issue: 3 Pages: 452-455

    • DOI

      10.1007/s13365-020-00845-0

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Progressive multifocal leukoencephalopathy during treatment with lenalidomide and elotuzumab for multiple myeloma2020

    • Author(s)
      Usui Yuta、Nakano Hiroto、Komatsu Junji、Nakamichi Kazuo、Saijo Masayuki、Takano Seiichiro、Kamiya Ken-ichi、Hamaguchi Tsuyoshi、Yamada Masahito
    • Journal Title

      Leukemia & Lymphoma

      Volume: 61 Issue: 9 Pages: 2234-2237

    • DOI

      10.1080/10428194.2020.1765237

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed
  • [Journal Article] JC virus granule cell neuronopathy associated with Ruxolitinib: A case report and review of the literature2020

    • Author(s)
      Nakayama Kentaro、Nakamura Masataka、Konishi Akiko、Kaneko Satoshi、Nakamichi Kazuo、Saijo Masayuki、Yakushiji Yusuke、Kusaka Hirofumi
    • Journal Title

      eNeurologicalSci

      Volume: 21 Pages: 100269-100269

    • DOI

      10.1016/j.ensci.2020.100269

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Inflammatory Cerebellar PML with a CD4/CD8 Ratio of 2.9 Showed a Favorable Prognosis in a Patient with Rheumatoid Arthritis2019

    • Author(s)
      Nishigori Ryusei、Warabi Yoko、Shishido-Hara Yukiko、Nakamichi Kazuo、Nakata Yasuhiro、Komori Takashi、Isozaki Eiji
    • Journal Title

      Internal Medicine

      Volume: 58 Issue: 22 Pages: 3323-3329

    • DOI

      10.2169/internalmedicine.3038-19

    • NAID

      130007746068

    • ISSN
      0918-2918, 1349-7235
    • Year and Date
      2019-11-15
    • Related Report
      2019 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Simultaneous Development of Progressive Multifocal Leukoencephalopathy and Cryptococcal Meningitis during Methotrexate and Infliximab Treatment2019

    • Author(s)
      Nosaki Yasunobu、Ohyama Ken、Watanabe Maki、Yokoi Takamasa、Nakamichi Kazuo、Saijo Masayuki、Miura Yoshiharu、Iwai Katsushige
    • Journal Title

      Internal Medicine

      Volume: 58 Issue: 18 Pages: 2703-2709

    • DOI

      10.2169/internalmedicine.2570-18

    • NAID

      130007706955

    • ISSN
      0918-2918, 1349-7235
    • Year and Date
      2019-09-15
    • Related Report
      2019 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Improving detection of JC virus by ultrafiltration of cerebrospinal fluid before polymerase chain reaction for the diagnosis of progressive multifocal leukoencephalopathy2019

    • Author(s)
      Nakamichi Kazuo、Kawamoto Michi、Ishii Junko、Saijo Masayuki
    • Journal Title

      BMC Neurology

      Volume: 19 Issue: 1

    • DOI

      10.1186/s12883-019-1476-2

    • Related Report
      2019 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Probable progressive multifocal leukoencephalopathy-immune reconstitution inflammatory syndrome with immunosuppressant dose reduction following lung transplantation: a case report and literature review2019

    • Author(s)
      Ishii Kazuhiro、Yamamoto Fumiko、Homma Shinsuke、Okada Yoshinori、Nakamichi Kazuo、Saijo Masayuki、Tamaoka Akira
    • Journal Title

      BMC Neurology

      Volume: 19 Issue: 1

    • DOI

      10.1186/s12883-019-1493-1

    • NAID

      120007127651

    • Related Report
      2019 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Successful treatment of non-HIV progressive multifocal leukoencephalopathy: case report and literature review2019

    • Author(s)
      Hamaguchi Mai、Suzuki Keisuke、Fujita Hiroaki、Uzuka Takeo、Matsuda Hadzki、Shishido-Hara Yukiko、Arai Satoko、Nakamura Toshiki、Kikuchi Shigeru、Nakamichi Kazuo、Saijo Masayuki、Hirata Koichi
    • Journal Title

      Journal of Neurology

      Volume: 267 Issue: 3 Pages: 731-738

    • DOI

      10.1007/s00415-019-09629-x

    • Related Report
      2019 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] A Punctate Magnetic Resonance Imaging Pattern in a Patient with Systemic Lupus Erythematosus Is an Early Sign of Progressive Multifocal Leukoencephalopathy: A Clinicopathological Study2018

    • Author(s)
      Ishii J, Shishido-Hara Y, Kawamoto M, Fujiwara S, Imai Y, Nakamichi K, Kohara N
    • Journal Title

      Internal Medicine

      Volume: 57 Issue: 18 Pages: 2727-2734

    • DOI

      10.2169/internalmedicine.0696-17

    • NAID

      130007484368

    • ISSN
      0918-2918, 1349-7235
    • Year and Date
      2018-09-15
    • Related Report
      2018 Research-status Report 2017 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] A loop-mediated isothermal amplification assay for the detection and quantification of JC polyomavirus in cerebrospinal fluid: a diagnostic and clinical management tool and technique for progressive multifocal leukoencephalopathy.2018

    • Author(s)
      Kinoshita H, Nakamichi K, Lim CK, Takayama-Ito M, Wang L, Iizuka I, Kurane I, Saijo M.
    • Journal Title

      Virology Journal

      Volume: 15 Issue: 1 Pages: 136-136

    • DOI

      10.1186/s12985-018-1046-z

    • Related Report
      2018 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Progressive multifocal leukoencephalopathy associated with thymoma with immunodeficiency: a case report and literature review.2018

    • Author(s)
      Tatsuya Ueno, Nobuyuki Sato, Tomoya Kon, Rie Haga, Jin-ichi Nunomura, Kazuo Nakamichi, Masayuki Saijo, Masahiko Tomiyama
    • Journal Title

      BMC Neurology

      Volume: 18 Issue: 1 Pages: 37-37

    • DOI

      10.1186/s12883-018-1041-4

    • Related Report
      2018 Research-status Report 2017 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Fingolimod-associated PML with mild IRIS in MS2017

    • Author(s)
      Nishiyama Shuhei、Misu Tatsuro、Shishido-Hara Yukiko、Nakamichi Kazuo、Saijo Masayuki、Takai Yoshiki、Takei Kentarou、Yamamoto Naoki、Kuroda Hiroshi、Saito Ryuta、Watanabe Mika、Tominaga Teiji、Nakashima Ichiro、Fujihara Kazuo、Aoki Masashi
    • Journal Title

      Neurology - Neuroimmunology Neuroinflammation

      Volume: 5 Issue: 1

    • DOI

      10.1212/nxi.0000000000000415

    • Related Report
      2017 Research-status Report
    • Peer Reviewed / Open Access
  • [Presentation] JC virus detection methods in the cerebrospinal fluid for PML-diagnosis; past, present, and future2019

    • Author(s)
      Masayuki Saijo, Kazuo Nakamichi
    • Organizer
      第60回日本神経学会学術大会
    • Related Report
      2019 Research-status Report
    • Invited
  • [Presentation] 日本国内発症進行性多巣性白質脳症の疫学調査と解析2019

    • Author(s)
      三浦義治、小佐見光樹、阿江竜介、中村好一、濱口毅、中道一生、高橋健太、鈴木忠樹、高橋和也、雪竹基弘、野村恭一、原田雅史、三條伸夫、船田信顕、岸田修二、西條政幸、水澤英洋、山田正仁
    • Organizer
      第60回日本神経学会学術大会
    • Related Report
      2019 Research-status Report
  • [Presentation] 成人T細胞白血病を背景に入院時頭部MRIで急性炎症性脱髄性疾患が疑われたが、脳生検にて進行性多巣性白質脳症と診断された1例2019

    • Author(s)
      徳井啓介、丹羽淳一、林未久、比嘉智子、中道一生、西條政幸、吉田真理、道勇学
    • Organizer
      第60回日本神経病理学会総会学術研究会
    • Related Report
      2019 Research-status Report
  • [Presentation] 多発性骨髄腫に対するレナリドミド及びエロツズマブの併用療法中に発症した進行性多巣性白質脳症(PML)の1例2019

    • Author(s)
      碓井雄大、中野博人、小松潤史、中道一生、髙野誠一郎、神谷健一、浜口毅、山田正仁
    • Organizer
      第24回日本神経感染症学会学術大会
    • Related Report
      2019 Research-status Report
  • [Presentation] メフロキン、ミルタザピン、リスペリドン併用療法で良好な経過をとった非AIDS-PMLの3例2019

    • Author(s)
      春日一希、星野優美、池田淳司、大橋信彦、中道一生、関島良樹
    • Organizer
      第24回日本神経感染症学会学術大会
    • Related Report
      2019 Research-status Report
  • [Presentation] 慢性リンパ性白血病に対するリツキシマブ/ベンダムスチン治療終了から半年後に進行性多巣性白質脳症(PML)を発症した82歳男性例2019

    • Author(s)
      水本悠希、大石真莉子、清水文崇、田中信一郎、中道一生、神田隆
    • Organizer
      第24回日本神経感染症学会学術大会
    • Related Report
      2019 Research-status Report
  • [Presentation] 抗ドナー抗体陽性の生体肝移植後に発症した進行性多巣性白質脳症の1例2019

    • Author(s)
      江頭柊平、角元利行、作石かおり、久保田暁、岩田淳、中道一生、西條政幸、戸田達史
    • Organizer
      第24回日本神経感染症学会学術大会
    • Related Report
      2019 Research-status Report
  • [Presentation] Meet the experts of NIID 6: PMLについて2019

    • Author(s)
      中道一生
    • Organizer
      第24回日本神経感染症学会学術大会
    • Related Report
      2019 Research-status Report
    • Invited
  • [Presentation] 日本国内発症PMLサーベイランス疫学調査と解析2019

    • Author(s)
      三浦義治、中道一生、小佐見光樹、阿江竜介、濱口毅、中村好一、西條政幸、山田正仁
    • Organizer
      第24回日本神経感染症学会学術大会
    • Related Report
      2019 Research-status Report
  • [Presentation] 培養細胞内のPML型JCポリオーマウイルスの複製2019

    • Author(s)
      奴久妻聡一、奴久妻智代子、亀岡正典、杉浦重樹、中道一生、田崎隆史、日高興士、竹上勉
    • Organizer
      第67回日本ウイルス学会学術集会
    • Related Report
      2019 Research-status Report
  • [Presentation] 自己免疫疾患を背景として生じる進行性多巣性白質脳症の実験室サーベイランス2019

    • Author(s)
      中道一生、西條政幸
    • Organizer
      第67回日本ウイルス学会学術集会
    • Related Report
      2019 Research-status Report
  • [Presentation] 頭部MRIで小脳、脳幹部に病変が局在し肺胞低換気を生じた進行性多巣性白質脳症の1剖検例2019

    • Author(s)
      下田学、矢崎夏美、廣瀬友城、中野滋文、諸井文子、高杉知明、堀場昌英、芳賀孝之、太田康男、末廣大知、高尾昌樹、中道一生、西條政幸
    • Organizer
      第33回日本エイズ学会学術集会
    • Related Report
      2019 Research-status Report
  • [Presentation] 進行性多巣性白質脳症が疑われた自己免疫疾患患者の脳脊髄液におけるJCウイルスゲノムDNAの検出2018

    • Author(s)
      中道一生、西條政幸
    • Organizer
      第23回日本神経感染症学会学術大会
    • Related Report
      2018 Research-status Report
  • [Presentation] 進行性多巣性白質脳症の原因と診断2018

    • Author(s)
      中道 一生、西條政幸
    • Organizer
      第36回日本神経治療学会学術集会
    • Related Report
      2018 Research-status Report
    • Invited
  • [Presentation] 脳脊髄液中JCウイルスの超高感度リアルタイムPCR検査におけるCLIA認定プライマーおよびプローブの有用性2017

    • Author(s)
      中道一生、西條政幸
    • Organizer
      第22回日本神経感染症学会学術大会
    • Related Report
      2017 Research-status Report
  • [Presentation] 本邦における進行性多巣性白質脳症(PML)サーベイランスの現状-PMLサーベイランス委員会報告-2017

    • Author(s)
      三浦義治、中道一生、西條政幸、高橋健太、鈴木忠樹、阿江竜介、濱口毅、原由紀子、三條伸夫、雪竹基弘、岸田修二、澤洋文、奴久妻聡一、水澤英洋、山田正仁
    • Organizer
      第22回日本神経感染症学会学術大会
    • Related Report
      2017 Research-status Report
  • [Presentation] 画像・病理・遺伝子解析で悪性リンパ腫が疑われた、高度リンパ球浸潤を伴った進行性多巣性白質脳症の1例2017

    • Author(s)
      宍戸-原由紀子、松林純、中道一生、西條政幸、相澤仁志、秋元治朗、長尾俊孝
    • Organizer
      第22回日本神経感染症学会学術大会
    • Related Report
      2017 Research-status Report
  • [Presentation] 脳生検により診断した進行性多巣性白質脳症の長期生存例2017

    • Author(s)
      佐藤翔紀、白井慎一、高橋育子、加納崇裕、矢部一郎、遠藤知之、豊嶋崇徳、東海林菊太郎、宝金清博、松野吉宏、太田雅之、三浦義治、中道一生、西條政幸、佐々木秀直
    • Organizer
      第22回日本神経感染症学会学術大会
    • Related Report
      2017 Research-status Report
  • [Presentation] CPT11 prevents virus replication in JCI cells persistently infected with JC polyomavirus.2017

    • Author(s)
      Souichi Nukuzuma, Chiyoko Nukuzuma, Masanori Kameoka, Shigeki Sugiura, Kazuo Nakamichi, Takafumi Tasaki, Tsutomu Takegami
    • Organizer
      第65回日本ウイルス学会学術集会
    • Related Report
      2017 Research-status Report
  • [Presentation] Deep-sequence identification and role in virus replication of a JCV quasispecies in PML patients.2017

    • Author(s)
      Kenta Takahashi, Tsuyoshi Sekizuka, Hitomi Fukumoto, Kazuo Nakamichi, Tadaki Suzuki, Yuko Sato, Hideki Hasegawa, Makoto Kuroda, Harutaka Katano
    • Organizer
      第106回日本病理学会総会
    • Related Report
      2017 Research-status Report
  • [Presentation] 次世代シークエンサーが明らかにしたJCウイルスのゲノム変異とPMLの病態2017

    • Author(s)
      高橋健太、関塚剛史、福本瞳、中道一生、鈴木忠樹、佐藤由子、長谷川秀樹、黒田誠、片野晴隆
    • Organizer
      第58回日本神経病理学会総会学術研究会
    • Related Report
      2017 Research-status Report
  • [Presentation] Punctate lesions demonstrated as an early sign of progressive multifocal leukoencephalopathy in a patient with systemic lupus erythematosus: a clinico-pathological study.2017

    • Author(s)
      Junko Ishii, Michi Kawamoto, Satoru Fujiwara, Yukihiro Imai, Kazuo Nakamichi, Kenta Takahashi, Yukiko Shishido-Hara, Nobuo Kohara
    • Organizer
      XXIII World Congress of Neurology
    • Related Report
      2017 Research-status Report
    • Int'l Joint Research
  • [Presentation] Third Japanese case of fingolimod-associated PML in natalizumab naive MS: Coincidence or alarm bell?2017

    • Author(s)
      Jin Nakahara, Kenji Kufukihara, Mariko Tanikawa, Kazuo Nakamichi, Masayuki Saijo, Yoshiharu Miura, Hirokazu Fujiwara, Masahiro Jinzaki, Takahito Yoshizaki, Shigeaki Suzuki, Shinichi Takahashi, Norihiro Suzuki
    • Organizer
      7th Joint ECTRIMS ACTRIMS Meeting 2017
    • Related Report
      2017 Research-status Report
    • Int'l Joint Research

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Published: 2017-04-28   Modified: 2022-01-27  

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