SEKIGUCHI Satoshi

写真a

Affiliation

Faculty of Agriculture Department of Veterinary Science

Title

Associate Professor

External Link

Degree 【 display / non-display

  • Doctor (Veterinary Medical Sciences) ( 2007.3   The University of Tokyo )

Research Areas 【 display / non-display

  • Life Science / Veterinary medical science

 

Papers 【 display / non-display

  • A pooled testing system to rapidly identify cattle carrying the elite controller BoLA-DRB3*009:02 haplotype against bovine leukemia virus infection. Reviewed International coauthorship

    Notsu K, Daous HE, Mitoma S, Norimine J, Sekiguchi S

    HLA   99 ( 1 )   12 - 24   2021.11

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    Authorship:Corresponding author   Language:English   Publishing type:Research paper (scientific journal)   Publisher:HLA  

    As genetically resistant individuals, the “elite controllers” (ECs) of human immunodeficiency virus infection have been focused on as the keys to developing further functional treatments in medicine. In the livestock production field, identifying the ECs of bovine leukemia virus (BLV) infection in cattle is desired to stop BLV transmission chains on farms. Cattle carrying the bovine leukocyte antigen (BoLA)-DRB3*009:02 allele (DRB3*009:02) have a strong possibility of being BLV ECs. Most of cattle carrying this allele maintain undetectable BLV proviral loads and do not shed virus even when infected. BLV ECs can act as transmission barriers when placed between uninfected and infected cattle in a barn. To identify cattle carrying DRB3*009:02 in large populations more easily, we developed a pooled testing system. It employs a highly sensitive, specific real-time PCR assay and TaqMan MGB probes (DRB3*009:02-TaqMan assay). Using this system, we determined the percentage of DRB3*009:02-carrying cattle on Kyushu Island, Japan. Our pooled testing system detected cattle carrying the DRB3*009:02 allele from a DNA pool containing one DRB3*009:02-positive animal and 29 cattle with other alleles. Its capacity is sufficient for herd-level screening for DRB3*009:02-carrying cattle. The DRB3*009:02-TaqMan assay showed high-discriminative sensitivity and specificity toward DRB3*009:02, making it suitable for identifying DRB3*009:02-carrying cattle in post-screening tests on individuals. We determined that the percentage of DRB3*009:02-carrying cattle in Kyushu Island was 10.56%. With its ease of use and reliable detection, this new method strengthens the laboratory typing for DRB3*009:02-carrying cattle. Thus, our findings support the use of BLV ECs in the field.

    DOI: 10.1111/tan.14502

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  • Relationship between allelic heterozygosity in bola-drb3 and proviral loads in bovine leukemia virus-infected cattle Reviewed International coauthorship

    Daous H.E., Mitoma S., Elhanafy E., Huyen N.T., Ngan M.T., Notsu K., Kaneko C., Norimine J., Sekiguchi S.

    Animals   11 ( 3 )   1 - 14   2021.3

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    Authorship:Corresponding author   Language:English   Publishing type:Research paper (scientific journal)   Publisher:Animals  

    Enzootic bovine leukosis is a lethal neoplastic disease caused by bovine leukemia virus (BLV), belongs to family Retroviridae. The BLV proviral load (PVL) represents the quantity of BLV genome that has integrated into the host’s genome in BLV-infected cells. Bovine leukocyte antigen (BoLA) class II allelic polymorphisms are associated with PVLs in BLV-infected cattle. We sought to identify relationships between BoLA-DRB3 allelic heterozygosity and BLV PVLs among different cattle breeds. Blood samples from 598 BLV-infected cattle were quantified to determine their PVLs by real-time polymerase chain reaction. The results were confirmed by a BLV-enzyme-linked immunosorbent assay. Restriction fragment length polymorphism-polymerase chain reaction identified 22 BoLA-DRB3 alleles. Multivariate negative binomial regression modeling was used to test for associations between BLV PVLs and BoLA-DRB3 alleles. BoLA-DRB3.2*3, *7, *8, *11, *22, *24, and *28 alleles were significantly associated with low PVLs. BoLA-DRB3.2*10 was significantly associated with high PVLs. Some heterozygous allele combinations were associated with low PVLs (*3/*28, *7/*8, *8/*11, *10/*11, and *11/*16); others were associated with high PVLs (*1/*41, *10/*16, *10/*41, *16/*27, and *22/*27). Interestingly, the BoLA-DRB3.2*11 heterozygous allele was always strongly and independently associated with low PVLs. This is the first reported evidence of an association between heterozygous allelic combinations and BLV PVLs.

    DOI: 10.3390/ani11030647

    Scopus

  • The detection of long-lasting memory foot-and-mouth disease (FMD) virus serotype O-specific CD4<sup>+</sup> T cells from FMD-vaccinated cattle by bovine major histocompatibility complex class II tetramer Reviewed International coauthorship

    Mitoma S., Carr B.V., Harvey Y., Moffat K., Sekiguchi S., Charleston B., Norimine J., Seago J.

    Immunology   164 ( 2 )   266 - 278   2021

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    Language:English   Publishing type:Research paper (scientific journal)   Publisher:Immunology  

    Foot-and-mouth disease (FMD) is a highly contagious, economically devastating disease of cloven-hooved animals. The development of long-lasting effective FMD vaccines would greatly benefit the global FMD control programme. Deep analysis of adaptive immunity in cattle vaccinated against FMD is technically challenging due to the lack of species-specific tools. In this study, we aimed to identify CD4+ T-cell epitopes in the FMD virus (FMDV) capsid and to phenotype the CD4+ T cells that recognize them using bovine major histocompatibility complex (BoLA) class II tetramer. A BoLA class II tetramer based on the DRA/DRB3*020:02 allele and FMDV antigen-stimulated PBMCs from bovine vaccinates were used to successfully identify four epitopes in the FMDV capsid, three of which have not been previously reported; two epitopes were identified in the structural protein VP1, one in VP3 and one in VP4. Specificity of the three novel epitopes was confirmed by proliferation assay. All epitope-expanded T-cell populations produced IFN-γ in vitro, indicating a long-lasting Th1 cell phenotype after FMD vaccination. VP3-specific CD4+ T cells exhibited the highest frequency amongst the identified epitopes, comprising >0·004% of the CD4+ T-cell population. CD45RO+CCR7+ defined central memory CD4+ T-cell subpopulations were present in higher frequency in FMDV-specific CD4+ T-cell populations from FMD-vaccinated cattle ex vivo. This indicates an important role in maintaining cell adaptive immunity after FMD vaccination. Notably, FMDV epitope-loaded tetramers detected the presence of FMDV-specific CD4+ T cells in bovine PBMC more than four years after vaccination. This work contributes to our understanding of vaccine efficacy.

    DOI: 10.1111/imm.13367

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  • Quantitative risk assessment for the introduction of bovine leukemia virus-infected cattle using a cattle movement network analysis Reviewed International coauthorship

    Notsu K., Wiratsudakul A., Mitoma S., Daous H.E., Kaneko C., El-Khaiat H.M., Norimine J., Sekiguchi S.

    Pathogens   9 ( 11 )   1 - 12   2020.11

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    Authorship:Corresponding author   Language:English   Publishing type:Research paper (scientific journal)   Publisher:Pathogens  

    © 2020 by the authors. Licensee MDPI, Basel, Switzerland. The cattle industry is suffering economic losses caused by bovine leukemia virus (BLV) and enzootic bovine leukosis (EBL), the clinical condition associated with BLV infection. This pathogen spreads easily without detection by farmers and veterinarians due to the lack of obvious clinical signs. Cattle movement strongly contributes to the inter-farm transmission of BLV. This study quantified the farm-level risk of BLV introduction using a cattle movement analysis. A generalized linear mixed model predicting the proportion of BLV-infected cattle was constructed based on weighted in-degree centrality. Our results suggest a positive association between weighted in-degree centrality and the estimated number of introduced BLV-infected cattle. Remarkably, the introduction of approximately six cattle allowed at least one BLV-infected animal to be added to the farm in the worst-case scenario. These data suggest a high risk of BLV infection on farms with a high number of cattle being introduced. Our findings indicate the need to strengthen BLV control strategies, especially along the chain of cattle movement.

    DOI: 10.3390/pathogens9110903

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  • A descriptive survey of porcine epidemic diarrhea in pig populations in northern Vietnam. Reviewed International coauthorship

    Mai TN, Yamazaki W, Bui TP, Nguyen VG, Le Huynh TM, Mitoma S, Daous HE, Kabali E, Norimine J, Sekiguchi S

    Tropical animal health and production   2020.10

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    Authorship:Corresponding author   Language:English   Publishing type:Research paper (scientific journal)  

    DOI: 10.1007/s11250-020-02416-1

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Books 【 display / non-display

  • veterinary epidemiology

    ( Role: Contributor)

    2022.3 

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    Language:Japanese Book type:Textbook, survey, introduction

  • 動物衛生学

    髙井伸二,末吉益男,永幡肇,他( Role: Joint author)

    文永堂出版  2018.4 

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    Total pages:415   Responsible for pages:125-136   Language:Japanese Book type:Textbook, survey, introduction

MISC 【 display / non-display

  • Editorial: The Epidemiology, Diagnosis and Prevention of Infectious Diseases in Livestock Invited International coauthorship

    Sekiguchi S., Wiratsudakul A., Nguyen V.G.

    Frontiers in Veterinary Science   8   840635   2022.1

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    Authorship:Lead author   Language:English   Publishing type:Article, review, commentary, editorial, etc. (scientific journal)   Publisher:Frontiers in Veterinary Science  

    DOI: 10.3389/fvets.2021.840635

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  • 動物感染症の数理モデル Invited

    関口 敏

    現代化学   2020.7

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    Language:Japanese   Publishing type:Article, review, commentary, editorial, etc. (scientific journal)  

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  • 家畜伝染病の包括防疫ケアシステムの構築に関する研究 Invited

    関口 敏

    調査月報   2020.5

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    Language:Japanese   Publishing type:Article, review, commentary, editorial, etc. (scientific journal)  

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  • 特定疾病フリー動物に対する付加価値の定量化に関する研究 Invited Reviewed

    関口 敏

    畜産の情報   2019.8

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    Language:Japanese   Publishing type:Article, review, commentary, editorial, etc. (scientific journal)  

  • だから牛ウイルス性下痢ウイルス感染症は損をする Invited

    関口敏

    臨床獣医   2019.7

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    Language:Japanese   Publishing type:Article, review, commentary, editorial, etc. (scientific journal)  

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Presentations 【 display / non-display

  • 確率論的手法を用いた肉用牛の外部導入における 牛伝染性リンパ腫ウイルス感染のリスク評価 International coauthorship

    藤原未歩、牛谷雄一、野津昴亮、Hala El-Daous、芹田光玲、 三苫修也、乗峰潤三、関口敏

    第164回日本獣医学会 

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    Event date: 2021.9.7 - 2021.9.13

    Language:Japanese   Presentation type:Oral presentation (general)  

  • CADIC生物統計学講座

    関口 敏

    CADICリスク分析学 

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    Event date: 2022.3.22 - 2022.3.23

    Language:Japanese   Presentation type:Oral presentation (general)  

  • A pooled testing system to rapidly identify cattle carrying the elite controller BoLA-DRB3*009:02 haplotype against bovine leukemia virus infection Invited International coauthorship

    関口 敏

    宮崎大学若手研究者論文発表支援報告会 

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    Event date: 2022.3.14

    Language:Japanese   Presentation type:Public lecture, seminar, tutorial, course, or other speech  

  • SATREPS JCC meeting International coauthorship International conference

    関口 敏

    SATREPS JCC meeting 

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    Event date: 2022.3.11

    Language:English   Presentation type:Oral presentation (general)  

  • 90分でわかる牛ウイルス性下痢症 Invited

    関口 敏

    令和3年度家畜生産農場衛生対策事業​ 

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    Event date: 2022.2.18

    Language:Japanese   Presentation type:Oral presentation (invited, special)  

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Awards 【 display / non-display

  • Japan Award

    2021.11  

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    Award type:International academic award (Japan or overseas) 

  • 宮崎大学若手研究者論文発表支援

    2022.3   宮崎大学  

    関口敏

  • 第57回獣医疫学会学術集会優秀学会発表賞

    2021.3   獣医疫学会   決定論的手法を用いた肉用牛の外部導入における牛伝染性リンパ腫ウイルス感染のリスク評価

    藤原未歩,牛谷雄一,野津昂亮,Hala El-Daous,芹田光玲,三苫修也,乗峰潤三,関口敏

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    Award type:Award from Japanese society, conference, symposium, etc.  Country:Japan

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  • 宮崎銀行ふるさと振興助成事業 学術研究部門

    2020.1   宮崎銀行  

    関口 敏

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    Award type:Award from publisher, newspaper, foundation, etc.  Country:Japan

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  • Japan Award

    2019.11  

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    Award type:International academic award (Japan or overseas)  Country:Japan

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Grant-in-Aid for Scientific Research 【 display / non-display

  • 牛白血病ウイルスの抵抗性牛の簡易判別診断法の開発

    Grant number:21J23396  2021.04 - 2024.03

    独立行政法人日本学術振興会  特別研究員奨励費

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    Authorship:Principal investigator 

  • 牛白血病ウイルスの血中プロウイルス量と感染細胞数に関する研究

    Grant number:20K06413  2020.04 - 2024.03

    科学研究費補助金  基盤研究(C)

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    Authorship:Principal investigator 

    牛白血病ウイルス(BLV)は牛のリンパ球(B細胞)に感染し,宿主のDNA中にプロウイルスとして組み込まれる。そのため血中プロウイルス量は,感染細胞数に比例するといわれ,感染力を評価する指標として知られている。しかし,血中のプロウイルス量だけでは感染力を説明できない個体も少なくない。そこで本研究では,BLVの感染力を説明する「第2の関連因子」を同定することを目的とする。まず,感染力には感染細胞あたりのプロウイルスの挿入個数が影響しているという仮説の下,プロウイルスを高精度に測定する絶対定量法を確立する。次に,臨床検体を用いて血中プロウイルス量とプロウイルスの挿入個数の関係を明らかにする。最後に,プロウイルスの挿入個数が感染力に及ぼす影響をフィールド調査で分析する。本研究によって新たな関連因子が同定されれば,より正確に感染リスクを評価することが可能となる。

  • 豚流行性下痢の感染拡大要因の解明

    2015.04 - 2018.03

    科学研究費補助金  若手研究(B)

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    Authorship:Principal investigator 

    本年(2014年)、全国的に膨大な経済的被害を出した豚流行性下痢(PED)は未だに感染が拡大している状況にある。その一方で、発生農家に近接していてもウイルスの侵入を防いでいる非感染農場が存在することも周知の事実である。このことから、感染農場と非感染農場の飼養管理方法や防疫対策方法を比較すれば、ウイルスの感染拡大に関与するリスク因子と防御因子を同定することが可能と予測される。本研究では、能動的サーベイランスを用いてPEDウイルスの感染農場と非感染農場を特定し、その相違点を明らかにすることでPEDの感染拡大要因の解明を行う(具体的技術については計画と方法に記載)。本研究によって、PEDの感染拡大する要因が解明されれば、科学的根拠に基づいた効果的な防疫対策の立案が可能になると期待される。

  • 免疫系の攪乱によるC型肝炎ウイルスの持続感染化及び発症機序の解析とその制御

    2009.04 - 2011.03

    科学研究費補助金  特定領域研究

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    Authorship:Coinvestigator(s) 

    【目的】C型肝炎は国内で約200万人に及ぶ感染者が存在し、安全で効果的な治療法の開発が急務となっている。我々はHCV遺伝子組換えワクチニアウイルス(HCV-RVV)株を樹立し、HCV持続感染モデルマウスを用いて治療ワクチンとしての有用性を検討した。

    【方法】Cre/loxPシステムでHCV遺伝子を導入したTg(Cre/loxP/HCV-Tg)マウスと、IFN誘導性のCreを発現するTgマウスを交配させ、任意の時期にHCV遺伝子をスイッチング発現するTgマウス(Cre/loxP/HCV-MxCreTg)を作製した。HCV-RVVはHCVの構造蛋白質を主に発現するCN2、非構造蛋白質を発現するN25、全蛋白質を発現するCN5を用いた。これらHCV-RVVの治療効果を評価するために、HCV蛋白を持続的に発現した状態のTgマウスに単回皮内接種し、接種後1週および4週のマウスにおいて解析を行った。

    【成績】HCV-RVV接種後1週のTgマウス肝臓では各接種群でHCV蛋白の減少が認められなかったが、4週ではN25接種群が減少していた。またN25接種群では接種後1週で肝臓の索状構造や肝細胞のsteatosisなど、HCV特有の形態学的な異常の正常化が認められた。N25接種群においてTgマウスのCD4またはCD8を欠損させるとHCV蛋白減少効果はみられなかったが、HCV特有の形態学的な異常の改善が認められた。

    【結論】我々が樹立したTgマウスは慢性肝炎を発症させることができるHCV持続感染モデルは、HCVの持続感染化と宿主の免疫応答の関係を解析することを可能にした。さらに、HCV-RVV(N25)接種によりマウス肝臓におけるHCV蛋白の減少及び慢性肝炎症状の正常化が認められた。HCVの肝細胞からの除去にはCD4,CD8 T細胞が関与しているが、HCVによる肝細胞の形態学的異常はHCV蛋白の発現に依存するのではなく他のメカニズムが関与していることが示唆された。

  • C型肝炎ウイルス複製におけるスフィンゴ脂質の役割と動態変化・恒常性維持機構の解析

    2008.04 - 2011.03

    科学研究費補助金  新学術領域研究(研究課題提案型)

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    Authorship:Coinvestigator(s) 

    ヒト肝臓型キメラマウスを使用し、C型肝炎ウイルス(HCV)感染、スフィンゴ脂質合成阻害剤の処置の際の肝臓内脂質変化をLC/MSにより比較解析することで、HCVが感染することでスフィンゴ脂質代謝が亢進すること明らかにした。

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Other external funds procured 【 display / non-display

  • Risk analysis of antimicrobial resistance transmission at the wildlife-livestock-human interface in Zambia

    2017.04 - 2020.03

    JSPS RONPAKU Program 

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    Grant type:Competitive