Updated on 2026/09/29

写真a

 
MATSUOKA Kazuhiro
 
Organization
Graduate School of Medicine Assistant Professor
Graduate School
Graduate School of Medicine
Undergraduate School
School of Health Sciences
Title
Assistant Professor

Research Interests 9

  1. ユビキチン化

  2. 感染症

  3. 構造

  4. 無細胞タンパク質合成

  5. 生体防御

  6. コムギ無細胞系

  7. HIV

  8. ウイルス

  9. エイズ

Research Areas 4

  1. Life Science / Parasitology

  2. Life Science / Structural biochemistry

  3. Life Science / Systems genomics

  4. Life Science / Virology

Research History 6

  1. Nagoya University   Assistant Professor

    2026.9

  2. Aichi Gakuin University   School of Dentistry Department of Dentistry

    2024.10

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    Country:Japan

  3. 国立病院機構 名古屋医療センター   臨床研究センター 感染・免疫研究部   客員研究員

    2018.1 - 2026.8

  4. Ehime University   Proteo-Science Center, Division of Molecular Parasitology   Assistant Professor

    2014.4 - 2017.12

  5. 国立病院機構 名古屋医療センター   臨床研究センター 感染・免疫研究部   客員研究員(財団法人エイズ予防財団リサーチレジデント)

    2012.4 - 2014.3

  6. 国立病院機構 名古屋医療センター   臨床研究センター 感染・免疫研究部   ポスドク

    2011.4 - 2012.3

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Education 3

  1. Ehime University

    2008.4 - 2011.3

  2. Ehime University

    2006.4 - 2008.3

  3. Ehime University   Faculty of Engineering   Department of Applied Chemistry

    2002.4 - 2006.3

Professional Memberships 3

  1. THE JAPANESE SOCIETY FOR VIROLOGY

  2. THE JAPANESE SOCIETY FOR AIDS RESEARCH

  3. THE MOLECULAR BIOLOGY SOCIETY OF JAPAN

Committee Memberships 1

  1. 日本エイズ学会   代議員  

    2023.12   

Awards 8

  1. 2026年度 第36回 自然科学系学術研究助成 助成金

    2026.9   公益財団法人 大幸財団   HIV-2 Vifと抗ウイルスタンパク質APOBEC3の複合体形成機構の解明

  2. 2026年度 医学系研究助成(感染領域)

    2026.6   公益財団法人 武田科学振興財団   HIV-1 Vif依存的な宿主抗ウイルスタンパク質APOBEC3のユビキチン化機構の解明

    松岡和弘

  3. 第39回日本エイズ学会 学術集会 優秀演題賞受賞 【基礎部門】

    2025.12  

    松岡和弘

  4. 第 27 回 日本レトロウイルス研究会夏期セミナー(SRC2025)

    2025.7   Best Presentation Award

    松岡和弘

  5. 第38回日本エイズ学会 学術集会 優秀演題賞受賞

    2024.11  

    松岡和弘

  6. Journal of Biological Chemistry EDITORS’ PICK Article(筆頭著者)に選出

    2022.3  

    松岡和弘

  7. 第73回 国立病院総合医学会 ベストポスター賞

    2019.11  

    松岡和弘

  8. 第27回 分子病理学研究会優秀発表賞

    2008.8  

    松岡和弘

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Papers 29

  1. HIV-1 vif mediates ubiquitination of the proximal protomer in the APOBEC3H dimer to induce degradation. Reviewed International journal Open Access

    Katarzyna A Skorupka, Kazuhiro Matsuoka (co-first author), Bakar Hassan, Rodolfo Ghirlando, Vanivilasini Balachandran, Ting-Hua Chen, Kylie J Walters, Celia A Schiffer, Matthias Wolf, Yasumasa Iwatani, Hiroshi Matsuo

    Nature communications   Vol. 16 ( 1 ) page: 5879 - 5879   2025.7

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

    The APOBEC3 family of cytidine deaminases restricts retroviruses like HIV-1 by mutating viral DNA. HIV-1 evades this restriction by producing Vif, which recruits the Cullin-5 (CUL5) E3 ubiquitin ligase complex to promote APOBEC3 degradation. Here we resolve key aspects of this counter-defense mechanism by determining a 3.6 Å cryo-EM structure of chimpanzee APOBEC3H (cpzA3H) in complex with HIV-1 Vif and three components of the CUL5 E3 ligase-CBFβ, EloB, and EloC (VCBC). The structure captures cpzA3H as an RNA-mediated dimer within the cpzA3H-VCBC complex, allowing us to examine the role of dimerization. We find that ubiquitination occurs specifically at two lysine residues on the Vif-proximal protomer, while the distal protomer remains unmodified. The structural model of the active cpzA3H-Vif-CUL5 E3 ligase holoenzyme reveals spatial preferences for ubiquitin transfer to the targeted lysine residues. These findings enhance our understanding of A3H degradation and suggest new antiviral strategies targeting this host-virus interface.

    DOI: 10.1038/s41467-025-60984-y

    Open Access

    PubMed

  2. The unique structure of the highly conserved PPLP region in HIV-1 Vif is critical for the formation of APOBEC3 recognition interfaces. Reviewed International journal Open Access

    Yasumasa Iwatani, Kazuhiro Matsuoka, Hirotaka Ode, Mai Kubota, Yoshihiro Nakata, Yuka Setoyama, Kanako Kojima, Mayumi Imahashi, Yoshiyuki Yokomaku

    mBio     page: e0333224   2025.1

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

    The human cellular cytidine deaminases APOBEC3s (A3s) inhibit virion infectivity factor (Vif)-deficient HIV-1 replication. However, virus-encoded Vifs abolish this defense system by specifically recruiting A3s to an E3 ubiquitin ligase complex to induce their degradation. The highly conserved Vif PPLP motif is critical for the Vif-mediated antagonism of A3s and is believed to be important for Vif multimerization. However, how the PPLP motif dictates the functions of Vif remains unclear. Here, we aimed to elucidate this mechanism using biochemical and structural biology approaches. First, we found that no stable Vif multimer complexes formed in our tandem coimmunoprecipitation assays. Next, a series of Vif truncation mutants were constructed, and the short α-helix α6 just downstream of PPLP was found to be the smallest fragment essential for efficient A3G degradation in cells. In silico structural analysis suggested that PPLP-α6 adopts a stable L-shaped conformation when complexed in Vif/CBF-β and contributes to the structural integrity of Vif. In vitro ubiquitination assays with recombinant proteins confirmed that PPLP-α6 is necessary to form the functional complex of the E3 ligase adaptor of Vif/CBF-β/elongin B/elongin C. Additionally, mutations of the highly conserved PPLP-α6 hydrophobic residues severely disrupted Vif function. In the Vif structure, PPLP-α6 is positioned behind α1-α2 that constitutes the A3-binding Vif interfaces. Therefore, both the PPLP motif and α6 play critical allosteric roles in maintaining the integrity of the A3 interaction interfaces. Our findings will also provide important data for the design of novel anti-HIV-1 compounds that disrupt the A3-binding Vif interfaces.IMPORTANCEThe APOBEC3 (A3) family enzymes potently block the replication of retroviruses, such as HIV-1. However, HIV-1 expresses Vif, a small multifaceted protein that binds and specifically eliminates A3s in infected cells via ubiquitination-proteasome degradation. Thus, A3-Vif interactions are attractive targets for anti-HIV-1 drug development. The Vif PPLP motif that is distal from these interfaces is necessary for A3 degradation; however, the mechanism by which PPLP participates in A3 degradation is unknown. In this study, we performed biochemical and structural biology analyses to elucidate the underlying mechanisms involved. We found that the PPLP motif, in addition to the short downstream fragment α6, forms a stable L-shaped conformation and acts as a scaffold for the A3 recognition interfaces. Importantly, mutations in α6 abolished Vif function to antagonize multiple A3 family enzymes. These findings provide important data for the development of novel HIV-1 inhibitors that utilize A3s as cellular defense enzymes.

    DOI: 10.1128/mbio.03332-24

    Open Access

    PubMed

  3. SARS-CoV-2 accessory protein ORF8 is secreted extracellularly as a glycoprotein homodimer. Reviewed International journal Open Access

    Kazuhiro Matsuoka, Nobuhiko Imahashi, Miki Ohno, Hirotaka Ode, Yoshihiro Nakata, Mai Kubota, Atsuko Sugimoto, Mayumi Imahashi, Yoshiyuki Yokomaku, Yasumasa Iwatani

    The Journal of biological chemistry   Vol. 298 ( 3 ) page: 101724 - 101724   2022.3

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

    ORF8 is an accessory protein encoded by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Consensus regarding the biological functions of ORF8 is lacking, largely because the fundamental characteristics of this protein in cells have not been determined. To clarify these features, we herein established an ORF8 expression system in 293T cells. Using this system, approximately 41% of the ORF8 expressed in 293T cells were secreted extracellularly as a glycoprotein homodimer with inter/intramolecular disulfide bonds. Intracellular ORF8 was sensitive to the glycosidase Endo H, whereas the secreted portion was Endo-H-resistant, suggesting that secretion occurs via a conventional pathway. Additionally, immunoblotting analysis showed that the total amounts of the major histocompatibility complex class Ι (MHC-I), angiotensin-converting enzyme 2 (ACE2), and SARS-CoV-2 spike (CoV-2 S) proteins coexpressed in cells were not changed by the increased ORF8 expression, although FACS analysis revealed that the expression of the cell surface MHC-I protein, but not that of ACE2 and CoV-2 S proteins, was reduced by ORF8 expression. Finally, we demonstrate by RNA-seq analysis that ORF8 had no significant stimulatory effects in human primary monocyte-derived macrophages (MDMs). Taken together, our results provide fundamental evidence that the ORF8 glycoprotein acts as a secreted homodimer, and its functions are likely associated with the intracellular transport and/or extracellular signaling in SARS-CoV-2 infection.

    DOI: 10.1016/j.jbc.2022.101724

    Open Access

    PubMed

  4. Antibody-like proteins that capture and neutralize SARS-CoV-2. Reviewed International journal Open Access

    T Kondo, Y Iwatani, K Matsuoka, T Fujino, S Umemoto, Y Yokomaku, K Ishizaki, S Kito, T Sezaki, G Hayashi, H Murakami

    Science advances   Vol. 6 ( 42 )   2020.10

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

    To combat severe acute respiratory syndrome-related coronavirus 2 (SARS-CoV-2) and any unknown emerging pathogens in the future, the development of a rapid and effective method to generate high-affinity antibodies or antibody-like proteins is of critical importance. We here report high-speed in vitro selection of multiple high-affinity antibody-like proteins against various targets including the SARS-CoV-2 spike protein. The sequences of monobodies against the SARS-CoV-2 spike protein were successfully procured within only 4 days. Furthermore, the obtained monobody efficiently captured SARS-CoV-2 particles from the nasal swab samples of patients and exhibited a high neutralizing activity against SARS-CoV-2 infection (half-maximal inhibitory concentration, 0.5 nanomolar). High-speed in vitro selection of antibody-like proteins is a promising method for rapid development of a detection method for, and of a neutralizing protein against, a virus responsible for an ongoing, and possibly a future, pandemic.

    DOI: 10.1126/sciadv.abd3916

    Open Access

    PubMed

  5. Simple Screening Method for Autoantigen Proteins Using the N-Terminal Biotinylated Protein Library Produced by Wheat Cell-Free Synthesis Reviewed Open Access

    Kazuhiro Matsuoka, Hiroaki Komori, Masato Nose, Yaeta Endo, Tatsuya Sawasaki

    JOURNAL OF PROTEOME RESEARCH   Vol. 9 ( 8 ) page: 4264 - 4273   2010.8

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

    DOI: 10.1021/pr9010553

    Open Access

    Web of Science

    PubMed

  6. Growth Transformation of B Cells by Epstein-Barr Virus Requires <i>IMPDH2</i> Induction and Nucleolar Hypertrophy Reviewed Open Access

    Atsuko Sugimoto, Takahiro Watanabe, Kazuhiro Matsuoka, Yusuke Okuno, Yusuke Yanagi, Yohei Narita, Seiyo Mabuchi, Hiroyuki Nobusue, Eiji Sugihara, Masaya Hirayama, Tomihiko Ide, Takanori Onouchi, Yoshitaka Sato, Teru Kanda, Hideyuki Saya, Yasumasa Iwatani, Hiroshi Kimura, Takayuki Murata

    Microbiology Spectrum     2023.7

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    Publishing type:Research paper (scientific journal)   Publisher:American Society for Microbiology  

    EBV infections cause nucleolar enlargement via the induction of IMPDH2, which are essential for B cell growth transformation by EBV. Although the significance of IMPDH2 induction and nuclear hypertrophy in the tumorigenesis of glioblastoma has been reported, EBV infection brings about the change quickly by using its transcriptional cofactor, EBNA2, and MYC. Moreover, we present here, for the novel, basic evidence that an IMPDH2 inhibitor, namely, MPA or MMF, can be used for EBV-positive posttransplant lymphoproliferative disorder (PTLD).

    DOI: 10.1128/spectrum.00440-23

    Open Access

  7. Cellular APOBEC3A deaminase drives mutations in the SARS-CoV-2 genome Reviewed International journal Open Access

    Yoshihiro Nakata, Hirotaka Ode, Mai Kubota, Takaaki Kasahara, Kazuhiro Matsuoka, Atsuko Sugimoto, Mayumi Imahashi, Yoshiyuki Yokomaku, Yasumasa Iwatani

    Nucleic Acids Research   Vol. 51 ( 2 ) page: 783 - 795   2023.1

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    Language:English   Publishing type:Research paper (scientific journal)   Publisher:Oxford University Press (OUP)  

    Abstract

    The number of genetic variations in the SARS-CoV-2 genome has been increasing primarily due to continuous viral mutations. Here, we report that the human APOBEC3A (A3A) cytidine deaminase plays a critical role in the induction of C-to-U substitutions in the SARS-CoV-2 genome. Bioinformatic analysis of the chronological genetic changes in a sequence database indicated that the largest UC-to-UU mutation signature, consistent with APOBEC-recognized nucleotide motifs, was predominant in single-stranded RNA regions of the viral genome. In SARS-CoV-2-infected cells, exogenous expression of A3A but not expression of other APOBEC proteins induced UC-to-UU mutations in viral RNA (vRNA). Additionally, the mutated C bases were often located at the tips in bulge or loop regions in the vRNA secondary structure. Interestingly, A3A mRNA expression was drastically increased by interferons (IFNs) and tumour necrosis factor-α (TNF-α) in epithelial cells derived from the respiratory system, a site of efficient SARS-CoV-2 replication. Moreover, the UC-to-UU mutation rate was increased in SARS-CoV-2 produced from lung epithelial cells treated with IFN-ß and TNF-α, but not from CRISPR/Cas9-based A3A knockout cells. Collectively, these findings demonstrate that A3A is a primary host factor that drives mutations in the SARS-CoV-2 RNA genome via RNA editing.

    DOI: 10.1093/nar/gkac1238

    Open Access

    PubMed

  8. 抗HIV因子APOBEC3Hの核酸結合能の評価 Reviewed

    松岡 和弘, 中田 佳宏, 大出 裕高, 大野 美希, 久保田 舞, 今橋 真弓, 横幕 能行, 岩谷 靖雅

    日本エイズ学会誌   Vol. 24 ( 4 ) page: 355 - 355   2022.11

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    Language:Japanese   Publishing type:Research paper (scientific journal)   Publisher:(一社)日本エイズ学会  

  9. Nanopore Sequencing for Characterization of HIV-1 Recombinant Forms. Reviewed International journal Open Access

    Mikiko Mori, Hirotaka Ode, Mai Kubota, Yoshihiro Nakata, Takaaki Kasahara, Urara Shigemi, Reiko Okazaki, Masakazu Matsuda, Kazuhiro Matsuoka, Atsuko Sugimoto, Atsuko Hachiya, Mayumi Imahashi, Yoshiyuki Yokomaku, Yasumasa Iwatani

    Microbiology spectrum   Vol. 10 ( 4 ) page: e0150722   2022.7

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

    High genetic diversity, including the emergence of recombinant forms (RFs), is one of the most prominent features of human immunodeficiency virus type 1 (HIV-1). Conventional detection of HIV-1 RFs requires pretreatments, i.e., cloning or single-genome amplification, to distinguish them from dual- or multiple-infection variants. However, these processes are time-consuming and labor-intensive. Here, we constructed a new nanopore sequencing-based platform that enables us to obtain distinctive genetic information for intersubtype RFs and dual-infection HIV-1 variants by using amplicons of HIV-1 near-full-length genomes or two overlapping half-length genome fragments. Repeated benchmark tests of HIV-1 proviral DNA revealed consensus sequence inference with a reduced error rate, allowing us to obtain sufficiently accurate sequence data. In addition, we applied the platform for sequence analyses of 9 clinical samples with suspected HIV-1 RF infection or dual infection according to Sanger sequencing-based genotyping tests for HIV-1 drug resistance. For each RF infection case, replicated analyses involving our nanopore sequencing-based platform consistently produced long consecutive analogous consensus sequences with mosaic genomic structures consisting of two different subtypes. In contrast, we detected multiple heterologous sequences in each dual-infection case. These results demonstrate that our new nanopore sequencing platform is applicable to identify the full-length HIV-1 genome structure of intersubtype RFs as well as dual-infection heterologous HIV-1. Since the genetic diversity of HIV-1 continues to gradually increase, this system will help accelerate full-length genome analysis and molecular epidemiological surveillance for HIV-1. IMPORTANCE HIV-1 is characterized by large genetic differences, including HIV-1 recombinant forms (RFs). Conventional genetic analyses require time-consuming pretreatments, i.e., cloning or single-genome amplification, to distinguish RFs from dual- or multiple-infection cases. In this study, we developed a new analytical system for HIV-1 sequence data obtained by nanopore sequencing. The error rate of this method was reduced to ~0.06%. We applied this system for sequence analyses of 9 clinical samples with suspected HIV-1 RF infection or dual infection, which were extracted from 373 cases of HIV patients based on our retrospective analysis of HIV-1 drug resistance genotyping test results. We found that our new nanopore sequencing platform is applicable to identify the full-length HIV-1 genome structure of intersubtype RFs as well as dual-infection heterologous HIV-1. Our protocol will be useful for epidemiological surveillance to examine HIV-1 transmission as well as for genotypic tests of HIV-1 drug resistance in clinical settings.

    DOI: 10.1128/spectrum.01507-22

    Open Access

    PubMed

  10. Monobodies with potent neutralizing activity against SARS-CoV-2 Delta and other variants of concern. Reviewed International journal Open Access

    Taishi Kondo, Kazuhiro Matsuoka, Shun Umemoto, Tomoshige Fujino, Gosuke Hayashi, Yasumasa Iwatani, Hiroshi Murakami

    Life science alliance   Vol. 5 ( 6 )   2022.6

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

    Neutralizing antibodies against the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are useful for patients' treatment of the coronavirus disease 2019 (COVID-19). We report here affinity maturation of monobodies against the SARS-CoV-2 spike protein and their neutralizing activity against SARS-CoV-2 B.1.1 (Pango v.3.1.14) as well as four variants of concern. We selected matured monobodies from libraries with multi-site saturation mutagenesis on the recognition loops through in vitro selection. One clone, the C4-AM2 monobody, showed extremely high affinity (K D < 0.01 nM) against the receptor-binding domain of the SARS-CoV-2 B.1.1, even in monomer form. Furthermore, the C4-AM2 monobody efficiently neutralized the SARS-CoV-2 B.1.1 (IC 50 = 46 pM, 0.62 ng/ml), and the Alpha (IC 50 = 77 pM, 1.0 ng/ml), Beta (IC 50 = 0.54 nM, 7.2 ng/ml), Gamma (IC 50 = 0.55 nM, 7.4 ng/ml), and Delta (IC 50 = 0.59 nM, 8.0 ng/ml) variants. The obtained monobodies would be useful as neutralizing proteins against current and potentially hazardous future SARS-CoV-2 variants.

    DOI: 10.26508/lsa.202101322

    Open Access

    PubMed

  11. Molecular epidemiological features of SARS-CoV-2 in Japan, 2020-1. Reviewed International journal Open Access

    Hirotaka Ode, Yoshihiro Nakata, Mami Nagashima, Masaki Hayashi, Takako Yamazaki, Hiroyuki Asakura, Jun Suzuki, Mai Kubota, Kazuhiro Matsuoka, Masakazu Matsuda, Mikiko Mori, Atsuko Sugimoto, Mayumi Imahashi, Yoshiyuki Yokomaku, Kenji Sadamasu, Yasumasa Iwatani

    Virus evolution   Vol. 8 ( 1 ) page: veac034   2022

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

    There were five epidemic waves of coronavirus disease 2019 in Japan between 2020 and 2021. It remains unclear how the domestic waves arose and abated. To better understand this, we analyzed the pangenomic sequences of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and characterized the molecular epidemiological features of the five epidemic waves in Japan. In this study, we performed deep sequencing to determine the pangenomic SARS-CoV-2 sequences of 1,286 samples collected in two cities far from each other, Tokyo Metropolis and Nagoya. Then, the spatiotemporal genetic changes of the obtained sequences were compared with the sequences available in the Global Initiative on Sharing All Influenza Data (GISAID) database. A total of 873 genotypes carrying different sets of mutations were identified in the five epidemic waves. Phylogenetic analysis demonstrated that sharp displacements of lineages and genotypes occurred between consecutive waves over the 2 years. In addition, a wide variety of genotypes were observed in the early half of each wave, whereas a few genotypes were detected across Japan during an entire wave. Phylogenetically, putative descendant genotypes observed late in each wave displayed regional clustering and evolution in Japan. The genetic diversity of SARS-CoV-2 displayed uneven dynamics during each epidemic wave in Japan. Our findings provide an important molecular epidemiological basis to aid in controlling future SARS-CoV-2 epidemics.

    DOI: 10.1093/ve/veac034

    Open Access

    PubMed

  12. SARS-CoV-2ゲノム配列に基づく分子疫学的動向とその特徴に関する考察(2020年3〜10月) Reviewed

    中田 佳宏, 大出 裕高, 久保田 舞, 松岡 和弘, 松田 昌和, 中筋 美穂, 森 美喜子, 今橋 真弓, 横幕 能行, 岩谷 靖雅

    感染症学雑誌   Vol. 95 ( 3 ) page: 293 - 300   2021.5

  13. Expression and Localization Profiles of Rhoptry Proteins in Plasmodium berghei Sporozoites Reviewed Open Access

    Naohito Tokunaga, Mamoru Nozaki, Mayumi Tachibana, Minami Baba, Kazuhiro Matsuoka, Takafumi Tsuboi, Motomi Torii, Tomoko Ishino

    Frontiers in Cellular and Infection Microbiology   Vol. 9   page: 316   2019.9

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    Publishing type:Research paper (scientific journal)  

    DOI: 10.3389/fcimb.2019.00316

    Open Access

    Scopus

    PubMed

  14. Rhoptry neck protein 11 has crucial roles during malaria parasite sporozoite invasion of salivary glands and hepatocytes. Reviewed International journal Open Access

    Sirasate Bantuchai, Mamoru Nozaki, Amporn Thongkukiatkul, Natcha Lorsuwannarat, Mayumi Tachibana, Minami Baba, Kazuhiro Matsuoka, Takafumi Tsuboi, Motomi Torii, Tomoko Ishino

    International journal for parasitology   Vol. 49 ( 9 ) page: 725 - 735   2019.8

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

    The malaria parasite sporozoite sequentially invades mosquito salivary glands and mammalian hepatocytes; and is the Plasmodium lifecycle infective form mediating parasite transmission by the mosquito vector. The identification of several sporozoite-specific secretory proteins involved in invasion has revealed that sporozoite motility and specific recognition of target cells are crucial for transmission. It has also been demonstrated that some components of the invasion machinery are conserved between erythrocytic asexual and transmission stage parasites. The application of a sporozoite stage-specific gene knockdown system in the rodent malaria parasite, Plasmodium berghei, enables us to investigate the roles of such proteins previously intractable to study due to their essentiality for asexual intraerythrocytic stage development, the stage at which transgenic parasites are derived. Here, we focused on the rhoptry neck protein 11 (RON11) that contains multiple transmembrane domains and putative calcium-binding EF-hand domains. PbRON11 is localised to rhoptry organelles in both merozoites and sporozoites. To repress PbRON11 expression exclusively in sporozoites, we produced transgenic parasites using a promoter-swapping strategy. PbRON11-repressed sporozoites showed significant reduction in attachment and motility in vitro, and consequently failed to efficiently invade salivary glands. PbRON11 was also determined to be essential for sporozoite infection of the liver, the first step during transmission to the vertebrate host. RON11 is demonstrated to be crucial for sporozoite invasion of both target host cells - mosquito salivary glands and mammalian hepatocytes - via involvement in sporozoite motility.

    DOI: 10.1016/j.ijpara.2019.05.001

    Open Access

    PubMed

  15. Discovery of 4-oxoquinolines, a new chemical class of anti-HIV-1 compounds. Reviewed International journal Open Access

    Shiroishi-Wakatsuki T, Maejima-Kitagawa M, Hamano A, Murata D, Sukegawa S, Matsuoka K, Ode H, Hachiya A, Imahashi M, Yokomaku Y, Nomura N, Sugiura W, Iwatani Y

    Antiviral research   Vol. 162   page: 101 - 109   2019.2

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

    Antiretroviral therapy (ART) against HIV-1 infection offers the promise of controlling disease progression and prolonging the survival of HIV-1-infected patients. However, even the most potent ART regimens available today cannot cure HIV-1. Because patients will be exposed to ART for many years, physicians and researchers must anticipate the emergence of drug-resistant HIV-1, potential adverse effects of the current drugs, and need for future drug development. In this study, we screened a small-molecule compound library using cell-based anti-HIV-1 assays and discovered a series of novel anti-HIV-1 compounds, 4-oxoquinolines. These compounds exhibited potent anti-HIV-1 activity (EC50 < 0.1 μM) with high selectivity indexes (CC50/EC50 > 2500) and favorable pharmacokinetic profiles in mice. Surprisingly, our novel compounds have a chemical backbone similar to the clinically used integrase (IN) strand transfer inhibitor (INSTI) elvitegravir, although they lack the crucial 3-carboxylate moiety needed for the common INSTI diketo motif. Indeed, the new 4-oxoquinoline derivatives have no detectable INSTI activity. In addition, various drug-resistant HIV-1 strains did not display cross resistance to these compounds. Interestingly, time-of-addition experiments indicated that the 4-oxoquinoline derivative remains its anti-HIV-1 activity even after the viral integration stage. Furthermore, the compounds significantly suppressed p24 antigen production in HIV-1 latently infected cells exposed with tumor necrosis factor alpha. These findings suggest that our 4-oxoquinoline derivatives with no 3-carboxylate moiety may become novel lead compounds in the development of anti-HIV-1 drugs.

    DOI: 10.1016/j.antiviral.2018.12.012

    Open Access

    PubMed

  16. Structural basis of chimpanzee APOBEC3H dimerization stabilized by double-stranded RNA. Reviewed International journal Open Access

    Matsuoka T, Nagae T, Ode H, Awazu H, Kurosawa T, Hamano A, Matsuoka K, Hachiya A, Imahashi M, Yokomaku Y, Watanabe N, Iwatani Y

    Nucleic acids research   Vol. 46 ( 19 ) page: 10368 - 10379   2018.11

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

    APOBEC3H (A3H) is a mammal-specific cytidine deaminase that potently restricts the replication of retroviruses. Primate A3Hs are known to exert key selective pressures against the cross-species transmission of primate immunodeficiency viruses from chimpanzees to humans. Despite recent advances, the molecular structures underlying the functional mechanisms of primate A3Hs have not been fully understood. Here, we reveal the 2.20-Å crystal structure of the chimpanzee A3H (cpzA3H) dimer bound to a short double-stranded RNA (dsRNA), which appears to be similar to two recently reported structures of pig-tailed macaque A3H and human A3H. In the structure, the dsRNA-binding interface forms a specialized architecture with unique features. The analysis of the dsRNA nucleotides in the cpzA3H complex revealed the GC-rich palindrome-like sequence preference for dsRNA interaction, which is largely determined by arginine residues in loop 1. In cells, alterations of the cpzA3H residues critical for the dsRNA interaction severely reduce intracellular protein stability due to proteasomal degradation. This suggests that cpzA3H stability is regulated by the dsRNA-mediated dimerization as well as by unknown cellular machinery through proteasomal degradation in cells. Taken together, these findings highlight unique structural features of primate A3Hs that are important to further understand their cellular functions and regulation.

    DOI: 10.1093/nar/gky676

    Open Access

    PubMed

  17. Identification of target proteins of clinical immunity to Plasmodium falciparum in a region of low malaria transmission Reviewed Open Access

    Hirokazu Sakamoto, Satoru Takeo, Eizo Takashima, Kazutoyo Miura, Bernard N. Kanoi, Takamasa Kaneko, Eun-Taek Han, Mayumi Tachibana, Kazuhiro Matsuoka, Jetsumon Sattabongkot, Rachanee Udomsangpetch, Tomoko Ishino, Takafumi Tsuboi

    Parasitology International   Vol. 67 ( 2 ) page: 203 - 208   2018.4

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    Language:English   Publishing type:Research paper (scientific journal)   Publisher:Elsevier Ireland Ltd  

    DOI: 10.1016/j.parint.2017.12.002

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    PubMed

  18. Structural Insights into HIV-1 Vif-APOBEC3F Interaction Reviewed Open Access

    Masaaki Nakashima, Hirotaka Ode, Takashi Kawamura, Shingo Kitamura, Yuriko Naganawa, Hiroaki Awazu, Shinya Tsuzuki, Kazuhiro Matsuoka, Michiko Nemoto, Atsuko Hachiya, Wataru Sugiura, Yoshiyuki Yokomaku, Nobuhisa Watanabe, Yasumasa Iwatani

    JOURNAL OF VIROLOGY   Vol. 90 ( 2 ) page: 1034 - 1047   2016.1

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

    DOI: 10.1128/JVI.02369-15

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  19. Quasispecies Analyses of the HIV-1 Near-full-length Genome With Illumina MiSeq Reviewed Open Access

    Hirotaka Ode, Masakazu Matsuda, Kazuhiro Matsuoka, co-first author, Atsuko Hachiya, Junko Hattori, Yumiko Kito, Yoshiyuki Yokomaku, Yasumasa Iwatani, Wataru Sugiura

    FRONTIERS IN MICROBIOLOGY   Vol. 6   page: 1258   2015.11

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

    DOI: 10.3389/fmicb.2015.01258

    Open Access

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  20. Natural polymorphism S119R of HIV-1 integrase enhances primary INSTI resistance Reviewed Open Access

    Atsuko Hachiya, Hirotaka Ode, Masakazu Matsuda, Yumiko Kito, Urara Shigemi, Kazuhiro Matsuoka, Junji Imamura, Yoshiyuki Yokomaku, Yasumasa Iwatani, Wataru Sugiura

    ANTIVIRAL RESEARCH   Vol. 119   page: 84 - 88   2015.7

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

    DOI: 10.1016/j.antiviral.2015.04.014

    Open Access

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  21. High-throughput synthesis of stable isotope-labeled transmembrane proteins for targeted transmembrane proteomics using a wheat germ cell-free protein synthesis system Reviewed

    Nobuaki Takemori, Ayako Takemori, Kazuhiro Matsuoka, Ryo Morishita, Natsuki Matsushita, Masato Aoshima, Hiroyuki Takeda, Tatsuya Sawasaki, Yaeta Endo, Shigeki Higashiyama

    MOLECULAR BIOSYSTEMS   Vol. 11 ( 2 ) page: 361 - 365   2015

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    DOI: 10.1039/c4mb00556b

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  22. APOBEC3G genotypes and proviral DNA hypermutations on HIV/AIDS disease progression in Thai and Cambodian children Reviewed

    Torsak Bunupuradah, Kazuhiro Matsuoka, Mayumi Imahashi, Yasumasa Iwatani, Jintanat Ananworanich, Thanyawee Puthanakit, Vonthanak Saphonn, Linda Aurpibul, Jiratchaya Sophonphan, Tetsuya Yagi, Praphan Phanuphak, Wataru Sugiura

    FUTURE VIROLOGY   Vol. 10 ( 12 ) page: 1267 - 1274   2015

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

    DOI: 10.2217/fvl.15.101

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    Scopus

  23. Profiling of Autoantibodies in Sera of Pancreatic Cancer Patients Reviewed

    Yosuke Nagayoshi, Masafumi Nakamura, Kazuhiro Matsuoka, Takao Ohtsuka, Yasuhisa Mori, Hiroshi Kono, Teppei Aso, Noboru Ideno, Shunichi Takahata, Akihide Ryo, Hiroyuki Takeda, Tetsuhide Ito, Yoshinao Oda, Yaeta Endo, Tatsuya Sawasaki, Masao Tanaka

    ANNALS OF SURGICAL ONCOLOGY   Vol. 21   page: 459 - 465   2014.6

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

    DOI: 10.1245/s10434-014-3574-0

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  24. Lack of Association between Intact/Deletion Polymorphisms of the APOBEC3B Gene and HIV-1 Risk Reviewed Open Access

    Mayumi Imahashi, Taisuke Izumi, Dai Watanabe, Junji Imamura, Kazuhiro Matsuoka, Hirotaka Ode, Takashi Masaoka, Kei Sato, Noriyo Kaneko, Seiichi Ichikawa, Yoshio Koyanagi, Akifumi Takaori-Kondo, Makoto Utsumi, Yoshiyuki Yokomaku, Takuma Shirasaka, Wataru Sugiura, Yasumasa Iwatani, Tomoki Naoe

    PLOS ONE   Vol. 9 ( 3 ) page: e92861   2014.3

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    DOI: 10.1371/journal.pone.0092861

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  25. Anti-interleukin-5 and multiple autoantibodies are associated with human atherosclerotic diseases and serum interleukin-5 levels Reviewed

    Tomoaki Ishigami, Kaito Abe, Ichiro Aoki, Shintaro Minegishi, Akihide Ryo, Satoko Matsunaga, Kazuhiro Matsuoka, Hiroyuki Takeda, Tatsuya Sawasaki, Satoshi Umemura, Yaeta Endo

    FASEB Journal   Vol. 27 ( 9 ) page: 3437 - 3445   2013.9

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    DOI: 10.1096/fj.12-222653

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  26. Novel approach to identifying autoantibodies in rheumatoid synovitis with a biotinylated human autoantigen library and the enzyme-labeled antigen method Reviewed

    Yasuyoshi Mizutani, Kazuhiro Matsuoka (co-first author), Hiroyuki Takeda, Kazuya Shiogama, Ken-ichi Inada, Kazue Hayakawa, Harumoto Yamada, Tatsuhiko Miyazaki, Tatsuya Sawasaki, Yaeta Endo, Yutaka Tsutsumi

    Journal of Immunological Methods   Vol. 387 ( 1-2 ) page: 57 - 70   2013.1

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

    DOI: 10.1016/j.jim.2012.09.011

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    PubMed

  27. Association of APOBEC3G genotypes and CD4 decline in Thai and Cambodian HIV-infected children with moderate immune deficiency Reviewed Open Access

    Torsak Bunupuradah, Mayumi Imahashi, Thatri Iampornsin, Kazuhiro Matsuoka, Yasumasa Iwatani, Thanyawee Puthanakit, Jintanat Ananworanich, Jiratchaya Sophonphan, Apicha Mahanontharit, Tomoki Naoe, Saphonn Vonthanak, Praphan Phanuphak, Wataru Sugiura

    AIDS RESEARCH AND THERAPY   Vol. 9 ( 1 ) page: 34   2012.11

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

    DOI: 10.1186/1742-6405-9-34

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    PubMed

  28. Specific In Situ Visualization of Plasma Cells Producing Antibodies against Porphyromonas gingivalis in Gingival Radicular Cyst: Application of the Enzyme-Labeled Antigen Method Reviewed Open Access

    Shinya Tsuge, Yasuyoshi Mizutani, Kazuhiro Matsuoka, Tatsuya Sawasaki, Yaeta Endo, Koji Naruishi, Hiroshi Maeda, Shogo Takashiba, Kazuya Shiogama, Ken-ichi Inada, Yutaka Tsutsumi

    JOURNAL OF HISTOCHEMISTRY & CYTOCHEMISTRY   Vol. 59 ( 7 ) page: 673 - 689   2011.7

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    DOI: 10.1369/0022155411408906

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  29. Biotinylated-sortase self-cleavage purification (BISOP) method for cell-free produced proteins Reviewed Open Access

    Satoko Matsunaga, Kazuhiro Matsuoka, Kouhei Shimizu, Yaeta Endo, Tatsuya Sawasaki

    BMC BIOTECHNOLOGY   Vol. 10   page: 42   2010.6

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

    DOI: 10.1186/1472-6750-10-42

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▼display all

MISC 33

  1. Molecular Epidemiological Insights into Transmission Trends in Nagoya Area Based on SARS-CoV-2 Genome Sequencing (Mar-Oct, 2020)

    中田佳宏, 中田佳宏, 大出裕高, 久保田舞, 松岡和弘, 松田昌和, 中筋美穂, 森美喜子, 森美喜子, 今橋真弓, 横幕能行, 岩谷靖雅, 岩谷靖雅

    感染症学雑誌(Web)   Vol. 95 ( 3 )   2021

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  2. Nanopore sequencingを利用したHIV-1のゲノム組換え体の解析

    森美喜子, 森美喜子, 大出裕高, 久保田舞, 中田佳宏, 中田佳宏, 杉本温子, 重見麗, 岡崎玲子, 松岡和弘, 松田昌和, 蜂谷敦子, 笠原嵩翔, 笠原嵩翔, 今橋真弓, 横幕能行, 岩谷靖雅, 岩谷靖雅

    日本エイズ学会誌   Vol. 23 ( 4 )   2021

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  3. 高速液体クロマトグラフィー-蛍光検出器による第二世代HIVインテグラーゼ阻害剤の血中濃度測定法の確立

    中田佳宏, 中田佳宏, 松岡和弘, 平野淳, 大出裕高, 今橋真弓, 蜂谷敦子, 中井正彦, 横幕能行, 岩谷靖雅, 岩谷靖雄

    日本エイズ学会誌   Vol. 21 ( 4 )   2019

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  4. スポロゾイトの唾液腺侵入に関わるロプトリータンパク質RAMAの作用機序の解明

    藤崎佳乃, 馬場みなみ, 野崎守, 橘真由美, 松岡和弘, 坪井敬文, 鳥居本美, 石野智子

    日本寄生虫学会大会プログラム・抄録集   Vol. 88th   2019

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  5. 抗HIV-1因子APOBEC3Hにおける多型変異R105Gの分子構造への影響

    大出裕高, 中田佳宏, 中田佳宏, 松岡和弘, 今橋真弓, 蜂谷敦子, 横幕能行, 岩谷靖雅, 岩谷靖雅

    日本エイズ学会誌   Vol. 21 ( 4 )   2019

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  6. 抗ウイルス因子APOBEC3Hの分子構造に対する多型変異R105Gの影響

    大出裕高, 中田佳宏, 中田佳宏, 松岡和弘, 今橋真弓, 蜂谷敦子, 横幕能行, 岩谷靖雅, 岩谷靖雅

    日本ウイルス学会学術集会プログラム・予稿集(Web)   Vol. 67th   2019

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  7. HPLC/蛍光検出機を用いた第二世代インテグラーゼ阻害剤の血中濃度の測定法の開発

    松岡和弘, 平野淳, 中田佳宏, 中田佳宏, 大出裕高, 蜂谷敦子, 今橋真弓, 中井正彦, 横幕能行, 岩谷靖雅, 岩谷靖雅

    国立病院総合医学会(Web)   Vol. 73rd   2019

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  8. HIV-1Vif依存的なAPOBEC3のユビキチン化におけるARIH2の機能的意義に関する研究

    松岡和弘, 大出裕高, 中田佳宏, 中田佳宏, 蜂谷敦子, 今橋真弓, 横幕能行, 岩谷靖雅, 岩谷靖雅

    日本ウイルス学会学術集会プログラム・予稿集(Web)   Vol. 67th   2019

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  9. 抗HIV因子APOBEC3Hタンパク質の構造解析

    松岡達矢, 松岡達矢, 永江峰幸, 大出裕高, 濱野章子, 松岡和弘, 蜂谷敦子, 今橋真弓, 横幕能行, 渡邉信久, 渡邉信久, 岩谷靖雅, 岩谷靖雅

    日本エイズ学会誌   Vol. 20 ( 4 )   2018

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  10. HIV-1感染におけるHIV-1 Vif PPLPモチーフ領域の役割

    松岡和弘, 濱野章子, 大出裕高, 松岡達矢, 松岡達矢, 助川明香, 蜂谷敦子, 今橋真弓, 横幕能行, 岩谷靖雅, 岩谷靖雅

    日本エイズ学会誌   Vol. 20 ( 4 )   2018

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  11. 持続感染した霊長類肝炎ウイルスの適応変異:ウイルスゲノム変異が及ぼす病態への影響

    東濃篤徳, 鈴木紗織, 森健一, 大出裕高, 松岡和弘, 片貝祐子, 岡林佐知, 槇昇, 岩谷靖雅, 杉浦亙, 明里宏文

    霊長類研究   Vol. 31 ( Supplement ) page: 81 - 82   2015.6

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    DOI: 10.14907/primate.31.0_81_2

    CiNii Research

    J-GLOBAL

  12. 霊長類ヘパチウイルス慢性感染後寛解におけるウイルスゲノム変異の意義 Reviewed

    東濃篤徳, 鈴木紗織, 大出裕高, 松岡和弘, 森健一, 片貝祐子, 岡林佐知, 槇昇, 岩谷靖雅, 杉浦亙, 明里宏文

    第63回日本ウイルス学会学術集会     2015

  13. サル指向性HIV-1のin vivoにおける増殖効率を上昇させる要因 Reviewed

    関洋平, 芳田剛, 齊藤暁, 松岡和弘, 大出裕高, 岩谷靖雅, 保富康宏, 俣野哲朗, 三浦智行, 杉浦亙, 明里宏文

    第62回日本実験動物学会総会     2015

  14. 小型霊長類において持続感染したヘパチウイルスゲノムの経時的変異 Reviewed

    東濃篤徳, 鈴木紗織, 森健一, 大出裕高, 松岡和弘, 片貝祐子, 岡林佐知, 槇昇, 岩谷靖雅, 杉浦亙, 明里宏文

    第62回日本実験動物学会学術集会     2015

  15. 慢性GBV-B感染におけるenvelope変異および液性免疫からの逃避 Reviewed

    鈴木紗織, 東濃篤徳, 森健一, 大出裕高, 松岡和弘, 岩谷靖雅, 杉浦亙, 片貝祐子, 槇昇, 明里宏文

    第63回日本ウイルス学会学術集会     2015

  16. Low humoral immune responses in New World Monkeys are associated with the persistent infection of primate hepatitis virus Reviewed

    Suzuki Saori, Higashino Atsunori, Mori Ken-ichi, Ode Hirotaka, Matsuoka Kazuhiro, Iwatani Yasumasa, Sugiura Wataru, Katakai Yuko, Maki Noboru, Akari Hirofumi

    Primate Research Supplement   Vol. 31   page: 78 - 78   2015

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    DOI: 10.14907/primate.31.0_78_1

    CiNii Research

  17. Genetic and immunological escape in persistent GBV-B infection Reviewed

    Saori Suzuki, Atsunori Higashino, Ken-ichi Mori, Hirotaka Ode, Kazuhiro Matsuoka, Yasumasa Iwatani, Wataru Sugiura, Yuko Katakai, Noboru Maki, Hirofumi Akari

    22nd International Symposium on Hepatitis C Virus and Related Viruses     2015

  18. 小型霊長類モデルを用いたヘパチウイルスの持続感染における慢性肝炎発症に影響するウイルスゲノム変異解析

    東濃篤徳, 鈴木紗織, 齊藤暁, 松岡和弘, 大出裕高, 片貝祐子, 岡林佐知, 森健一, 槇昇, 明里宏文

    日本実験動物学会総会講演要旨集   Vol. 61st   page: 267   2014.5

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    J-GLOBAL

  19. 小型霊長類において持続感染したGBV-Bの変異解析 Reviewed

    東濃篤徳, 鈴木紗織, 森健一, 大出裕高, 松岡和弘, 片貝祐子, 岡林佐知, 槇昇, 岩谷靖雅, 杉浦亙, 明里宏文

    第62回日本ウイルス学会学術集会     2014

  20. サル個体におけるサル指向性HIV-1の増殖効率を上昇させる要因 Reviewed

    芳田剛, 齊藤暁, 松岡和弘, 大出裕高, 岩谷靖雅, 杉浦亙, 保富康宏, 俣野哲朗, 三浦智行, 明里宏文

    第62回日本ウイルス学会学術集会     2014

  21. サル指向性HIV-1の感染個体における増殖効率を上昇させる要因 Reviewed

    芳田剛, 齊藤暁, 松岡和弘, 大出裕高, 岩谷靖雅, 杉浦亙, 保富康宏, 俣野哲朗, 三浦智行, 明里宏文

    第28回日本エイズ学会学術集会・総会     2014

  22. HIV-1 near full-length genome analysis by next-generation sequencing: evaluation of quasispecies and minority drug resistance

    H. Ode, K. Matsuoka, M. Matsuda, A. Hachiya, J. Hattori, Y. Yokomaku, Y. Iwatani, W. Sugiura

    ANTIVIRAL THERAPY   Vol. 19   page: A80 - A80   2014

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    Web of Science

  23. HIV‐1臨床分離株を用いたRilpivirine及びEtravirineに対する交差耐性変異に関する酵素学的な解析

    松岡和弘, 重見麗, 大出裕高, 蜂谷敦子, 服部純子, 森下了, 澤崎達也, 横幕能行, 岩谷靖雅, 杉浦亙

    日本エイズ学会誌   Vol. 15 ( 4 ) page: 472 - 472   2013.11

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    J-GLOBAL

  24. 本邦HIV-1感染患者におけるHIV-1 vifの分子遺伝学的解析

    村上理彦, 松岡和弘, 椎野禎一郎, 今橋真弓, 松田昌和, 横幕能行, 岩谷靖雅, 岩谷靖雅, 杉浦亙, 杉浦亙

    日本エイズ学会誌   Vol. 15 ( 4 )   2013

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  25. 宿主防御因子APOBEC3Bの遺伝子欠損によるHIV-1感染伝播・病勢への影響に関する研究

    今橋真弓, 今橋真弓, 泉泰輔, 渡邊大, 今村淳治, 松岡和弘, 正岡崇志, 佐藤佳, 金子典代, 市川誠一, 小柳義夫, 高折晃史, 内海眞, 横幕能行, 白阪琢磨, 直江知樹, 杉浦亙, 杉浦亙, 岩谷靖雅, 岩谷靖雅

    日本ウイルス学会学術集会プログラム・抄録集   Vol. 61st   2013

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  26. Complexity of cross-resistance mutation patterns in diarylpyrimidine non-nucleoside reverse transcriptase inhibitors rilpivirine and etravirine in clinical isolates

    K. Matsuoka, F. Tanabe, U. Shigemi, J. Hattori, H. Ode, T. Masaoka, R. Morishita, T. Sawasaki, Y. Yokomaku, Y. Iwatani, W. Sugiura

    ANTIVIRAL THERAPY   Vol. 18   page: A110 - A110   2013

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    Web of Science

  27. コムギ無細胞蛋白質合成系を利用したHIV‐1逆転写酵素のin vitro薬剤感受性解析法の開発

    松岡和弘, 田邊史子, 重見麗, 服部純子, 正岡崇志, 森下了, 澤崎達也, 横幕能行, 岩谷靖雅, 杉浦亙

    日本エイズ学会誌   Vol. 14 ( 4 ) page: 388 - 388   2012.11

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    J-GLOBAL

  28. SF-031-6 コムギ無細胞蛋白合成系を用いた自己抗体スクリーニング法による癌関連自己抗体の同定(SF-031 サージカルフォーラム(31)膵 基礎-2(病因,危険因子,発癌因子),第112回日本外科学会定期学術集会)

    永吉 洋介, 中村 雅史, 松岡 和弘, 安蘇 鉄平, 井手野 昇, 河野 博, 森 泰寿, 大塚 隆生, 高畑 俊一, 澤崎 達也, 田中 雅夫

    日本外科学会雑誌   Vol. 113 ( 2 ) page: 327 - 327   2012.3

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    CiNii Research

  29. HIV-1感染伝播・病勢に対するAPOBEC3B遺伝子型の影響に関する解析

    今橋真弓, 今橋真弓, 泉泰輔, 泉泰輔, 今村淳治, 松岡和弘, 金子典代, 市川誠一, 高折晃史, 内海眞, 横幕能行, 直江知樹, 杉浦亙, 杉浦亙, 岩谷靖雅, 岩谷靖雅

    日本エイズ学会誌   Vol. 14 ( 4 )   2012

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  30. Exploring novel diagnostic marker for breast cancer by autoantigen screening.

    H. Fujiki, H. Takeda, K. Matsuoka, Y. Miyagi, A. Yoshida, Y. Endo, T. Sawasaki

    MOLECULAR BIOLOGY OF THE CELL   Vol. 22   2011

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    Web of Science

  31. Development of in vitro enzymatic method for assessing susceptibility to HIV-1 reverse transcriptase inhibitors using a wheat-germ cell-free translation system

    MATSUOKA Kazuhiro, MASAOKA Takashi, TANABE Fumiko, MORISHITA Ryo, SAWASAKI Tatsuya, IWATANI Yasumasa, SUGIURA Wataru

    日本分子生物学会年会プログラム・要旨集(Web)   Vol. 34th   page: 2T18PII-10 (WEB ONLY)   2011

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    J-GLOBAL

  32. 高速免疫スクリーニングによる新規熱帯熱マラリア赤血球期ワクチン候補抗原の探索

    坂本寛和, 竹尾暁, 金子隆昌, 谷上弘恵, 松岡和弘, 橘真由美, 澤崎達也, JETSUMON Sattabongkot, 鳥居本美, 坪井敬文

    日本寄生虫学会大会プログラム・抄録集   Vol. 78th   page: 83   2009.2

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    Language:Japanese  

    J-GLOBAL

  33. 新規マラリアワクチン候補抗原探索へ向けたハイスループットスクリーニング法の開発

    坂本寛和, 竹尾暁, 松岡和弘, 橘真由美, 澤崎達也, 坪井敬文

    日本寄生虫学会大会プログラム・抄録集   Vol. 77th   page: 61   2008.3

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Research Project for Joint Research, Competitive Funding, etc. 6

  1. HIV-2 Vifと抗ウイルスタンパク質APOBEC3の複合体形成機構の解明

    2026.10 - 2028.3

    公益財団法人 大幸財団  2026年度 第36回 自然科学系学術研究助成  助成金

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    Authorship:Principal investigator 

  2. HIV-1 Vif依存的な宿主抗ウイルスタンパク質APOBEC3のユビキチン化機構の解明

    2026.9 - 2031.3

    公益財団法人 武田科学振興財団  2026年度 武田科学振興財団 医学系研究助成(感染領域)  助成金

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    Authorship:Principal investigator 

  3. Viral mimicryを制御する新規タンパク質のIFN-ß発現制御機構の解明

    2026.9 - 2027.3

    公益財団法人愛知県がん研究振興会  第51回がんその他の悪性新生物研究助成金  助成金

  4. APOBEC3Hの核酸結合を基盤とした抗ウイルス活性の分子機序の解明

    Grant number:23K06568  2023.4 - 2026.3

    科学研究費助成事業  基盤研究(C)

    松岡 和弘

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    Authorship:Principal investigator 

    Grant amount:\4680000 ( Direct Cost: \3600000 、 Indirect Cost:\1080000 )

    宿主防御因子APOBEC3(以下:A3)ファミリーは、ウイルス遺伝子である一本鎖核酸 (ssDNA、ssRNA)を標的として強力な抗レトロウイルス作用を持つことがわかってきた。 2018年に申請者らがA3Hの二本鎖核酸(dsRNA)を介した二量体構造を決定し、A3Hが一本鎖核酸にしか結合しないと考えられてきた定説を覆す発見をした。しかし、A3Hの分子特性および抗ウイルス作用の分子機序は未解明のままである。本研究では、A3Hの核酸結合能の観点で機能解析を行い、抗ウイルス作用の分子機序を解明することを目的とする。本研究により、A3ファミリーによる生体防御機構の更なる理解を目指す。
    これまでに申請者らは、二本鎖核酸(dsRNA)を介したA3Hの二量体構造を決定し、A3Hが一本鎖核酸(ssDNA、ssRNA)にしか結合しないと考えられてきた定説を覆す発見をしてきた。しかし、核酸を介したA3Hの分子特性および抗ウイルス作用の分子機序は未解明のままである。本研究では、生化学的解析法および構造解析技術を基盤に、A3Hの抗ウイルス作用の分子機構を解明することを目的とする。当該年度において、HIV-1 Vif/CBFb/ELOB/ELOC (VCBC)-A3H複合体に関して、核酸(RNA)との相互作用に着目して研究を実施し、以下の研究成果を得た。
    1)クライオ電子顕微鏡解析を用いて、3.8オングストロームの分解能でHIV-1 VCBC-A3H複合体構造の決定に成功した。そして、HIV-1 VCBC-A3H複合体が二量体を形成することが明らかになった。
    2)二量体形成は主にVif-dsRNA相互作用およびVif-Vif相互作用によって媒介されることを見出した。
    3)相互作用界面のアミノ酸の機能的意義について、Vif依存的なA3H分解アッセイで解析を行い、A3H分解に影響を及ぼす新たなVif残基を同定した(Vif-RNA相互作用: R15、L81、K160、P161、Vif-Vif相互作用: H42、Y44、P49、W70)。
    以上、これらの結果は、Vif-dsRNA相互作用がVCBC-A3H二量体構造の維持に役割を果たしていることを示唆しており、Vif依存的なA3Hのユビキチン化に重要であると考えられる。さらに、同様の相互作用がAPOBEC3ファミリーの一つであるA3G-Vif構造でも報告されており、Vif依存的なA3G分解に必須であることが示されている。これら報告と我々の結果は、RNAの存在がVif依存的なA3のユビキチン化の重要な特徴である可能性を示唆している。
    HIV-1 VCBC-A3H複合体構造を基盤としたVif依存的なA3Hユビキチン化の分子機構の論文(Skorupka, Matsuoka (co-first author) et al. Nat Commun. in press)を核酸(RNA)との相互作用の重要性も含めて報告することができたことは、当該分野において重要な知見を取得し学術論文として研究成果を公表できた点では順調に研究が進展したといえる。一方で、2024年度は当該論文の追加実験およびリバイズ実験で想定以上の時間を要してしまい、A3Hの核酸結合能と細胞内分布の観点で機能解析を行い抗ウイルス作用に与える影響に関しては進行が遅れている。以上の理由から、総じておおむね順調に進展していると判断した。
    独自に構築した生化学的解析法を用いて、各種核酸(ssDNA、 ssRNA、 dsRNA)の結合に必要なA3Hの結合領域を解析する。各種核酸の結合に必要なA3Hの領域を分子構造にマッピングして、A3Hの機能的な影響と意義を考察する。そして、蛍光顕微鏡を用いた細胞内局在解析でA3Hの細胞内局在化に必要な領域を決定し、分子構造にマッピングする。各種核酸の結合領域と細胞内局在に必要な領域について総合的に考察を行う。さらに、各種核酸の結合に必要な領域および細胞内局在化に必要な領域の変異型A3Hを用いて抗HIV活性を解析する。最終的に、どの種類の核酸に結合したA3Hが何処に局在してどのように抗ウイルス作用を担っているのかを明らかにして行く予定である。

  5. The mechanism of complex formation between HIV-1 Vif and host factor APOBEC3

    Grant number:20K07533  2020.4 - 2023.3

    Grants-in-Aid for Scientific Research  Grant-in-Aid for Scientific Research (C)

    MATSUOKA Kazuhiro

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    Authorship:Principal investigator 

    Grant amount:\4290000 ( Direct Cost: \3300000 、 Indirect Cost:\990000 )

    HIV-1 Vif is an accessory protein, that antagonizes the antiviral effects of host restriction factor APOBEC3H (A3H) proteins for viral replication in the host. Vif hijacks a host cellular Cullin-5 (CUL5) E3 ubiquitin ligase complex (Vif/CBF-β/ELOB/ELOC/CUL5 complex) to target A3H proteins for ubiquitination and proteasomal degradation. This study aimed to determine the structure of the Vif-A3H complex and elucidate the mechanism of complex formation of the Vif-A3H complex and the Vif-dependent ubiquitination of A3H at the atomic and molecular levels.

  6. ヒトプロテインアレイを用いた新規抗HIV宿主防御因子の網羅的な探索と解析

    Grant number:18K14685   2018.4 - 2020.3

    科学研究費補助金 若手研究 

    松岡和弘

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    Authorship:Principal investigator  Grant type:Competitive

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KAKENHI (Grants-in-Aid for Scientific Research) 3

  1. APOBEC3Hの核酸結合を基盤とした抗ウイルス活性の分子機序の解明

    Grant number:23K06568  2023.4 - 2026.3

    日本学術振興会  科学研究費助成事業  基盤研究(C)

    松岡 和弘

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    Authorship:Principal investigator 

    Grant amount:\4680000 ( Direct Cost: \3600000 、 Indirect Cost:\1080000 )

  2. HIV-1 Vifと宿主防御因子APOBEC3の複合体形成機構の解明 International coauthorship

    Grant number:20K07533  2020.4 - 2023.3

    日本学術振興会  科学研究費助成事業  基盤研究(C)

    松岡 和弘

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    Authorship:Principal investigator  Grant type:Competitive

    Grant amount:\4290000 ( Direct Cost: \3300000 、 Indirect Cost:\990000 )

  3. Biochemical and functional analysis of anti-HIV host factor

    Grant number:18K14685  2018.4 - 2020.3

    Grants-in-Aid for Scientific Research  Grant-in-Aid for Early-Career Scientists

    Matsuoka Kazuhiro

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    Authorship:Principal investigator 

    Grant amount:\4160000 ( Direct Cost: \3200000 、 Indirect Cost:\960000 )

    The HIV-1 Vif is an accessory protein, that antagonizes the antiviral effects of host restriction factor APOBEC3 proteins for viral replication in its corresponding host. Vif hijacks the cellular CUL5 complex to form a virus-specific E3 ubiquitin ligase complex that targets APOBEC3 proteins for ubiquitination and proteasomal degradation. In this study, we are successful to develop in vitro reconstituted ubiquitination assay for functional analysis of Vif-mediated ubiquitination of APOBEC3. We clarified the molecular mechanisms for efficient and specific antagonism of APOBEC3 through HIV-1 Vif-mediated ubiquitination machinery.

Industrial property rights 1

  1. 抗原検索法及び抗体検出法

    堤 寛, 水谷 泰嘉, 遠藤 弥重太, 澤崎 達也, 松岡 和弘

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    Applicant:学校法人藤田学園, 国立大学法人愛媛大学

    Application no:特願2010-079277  Date applied:2010.3

    Announcement no:特開2011-209224  Date announced:2011.10

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Teaching Experience (Off-campus) 4

  1. こころと体

    (Ehime University)

  2. 寄生虫学 (実習)

    (Ehime University)

  3. 生化学(講義)

    (名古屋医療センター附属名古屋看護助産学校)

  4. 生命の分子的基盤(生化学実習)

    (愛知学院大学歯学部)