2024/12/22 更新

写真a

オトグロ　テルヒメ
乙黒　光姫
OTOGURO Teruhime
所属
教育研究院 医歯学系 特任助教
医歯学総合研究科 特任助教
職名
特任助教
外部リンク

学位

  • 博士（医科学） （ 2020年3月   山梨大学 ）

経歴（researchmap）

  • 新潟大学   大学院医歯学総合研究科   特任助教

    2022年4月 - 現在

    　 詳細を見る

  • 一般社団法人予防衛生協会   試験検査部   研究員

    2020年6月 - 2022年3月

    　 詳細を見る

経歴

  • 新潟大学   医歯学総合研究科   特任助教

    2022年4月 - 現在

  • 新潟大学   教育研究院 医歯学系   特任助教

    2022年4月 - 現在

 

論文

  • Changing Seasonality of Influenza in the Post-COVID Era in Japan.

    Keita Wagatsuma, Teruhime Otoguro

    JMA journal   7 ( 1 )   138 - 139   2024年1月

    　詳細を見る

    記述言語：英語   掲載種別：研究論文（学術雑誌）  

    DOI： 10.31662/jmaj.2023-0150

    PubMed

    researchmap

  • Molecular Epidemiology of Respiratory Syncytial Virus during 2019-2022 and Surviving Genotypes after the COVID-19 Pandemic in Japan. 国際誌

    Sayaka Yoshioka, Wint Wint Phyu, Keita Wagatsuma, Takao Nagai, Yasuko Sano, Kiyosu Taniguchi, Nobuo Nagata, Kazuhiko Tomimoto, Isamu Sato, Harumi Kaji, Ken Sugata, Katsumi Sugiura, Naruo Saito, Satoshi Aoki, Eitaro Suzuki, Yasushi Shimada, Hirotsune Hamabata, Irina Chon, Teruhime Otoguro, Hisami Watanabe, Reiko Saito

    Viruses   15 ( 12 )   2023年12月

    　詳細を見る

    記述言語：英語   掲載種別：研究論文（学術雑誌）  

    To evaluate the changes in respiratory syncytial virus (RSV) collected between 2019 and 2022, we analyzed RSV-A and RSV-B strains from various prefectures in Japan before and after the COVID-19 pandemic. RT-PCR-positive samples collected from children with rapid test positivity at outpatient clinics in 11 prefectures in Japan were sequenced for the ectodomain of the G gene to determine the genotype. Time-aware phylogeographic analyses were performed using the second hypervariable region (HVR) of the G gene from 2012 to 2022. Of 967 samples, 739 (76.4%) were found to be RSV-positive using RT-PCR. RSV peaked in September 2019 but was not detected in 2020, except in Okinawa. Nationwide epidemics occurred with peaks in July 2021 and 2022. The genotype remained the same, ON1 for RSV-A and BA9 for RSV-B during 2019-2022. Phylogeographic analysis of HVR revealed that at least seven clusters of RSV-A had circulated previously but decreased to two clusters after the pandemic, whereas RSV-B had a single monophyletic cluster over the 10 years. Both RSV-A and RSV-B were transferred from Okinawa into other prefectures after the pandemic. The RSV epidemic was suppressed due to pandemic restrictions; however, pre-pandemic genotypes spread nationwide after the pandemic.

    DOI： 10.3390/v15122382

    PubMed

    researchmap

  • Whole-Genome Analysis of Influenza A(H3N2) and B/Victoria Viruses Detected in Myanmar during the COVID-19 Pandemic in 2021. 国際誌

    Irina Chon, Reiko Saito, Yadanar Kyaw, Moe Myat Aye, Swe Setk, Wint Wint Phyu, Keita Wagatsuma, Jiaming Li, Yuyang Sun, Teruhime Otoguro, Su Mon Kyaw Win, Sayaka Yoshioka, Nay Chi Win, Lasham Di Ja, Htay Htay Tin, Hisami Watanabe

    Viruses   15 ( 2 )   2023年2月

    　詳細を見る

    記述言語：英語   掲載種別：研究論文（学術雑誌）  

    An influenza circulation was observed in Myanmar between October and November in 2021. Patients with symptoms of influenza-like illness were screened using rapid diagnostic test (RDT) kits, and 147/414 (35.5%) upper respiratory tract specimens presented positive results. All RDT-positive samples were screened by a commercial multiplex real-time polymerase chain reaction (RT-PCR) assay, and 30 samples positive for influenza A(H3N2) or B underwent further typing/subtyping for cycle threshold (Ct) value determination based on cycling probe RT-PCR. The majority of subtyped samples (n = 13) were influenza A(H3N2), while only three were B/Victoria. Clinical samples with low Ct values obtained by RT-PCR were used for whole-genome sequencing via next-generation sequencing technology. All collected viruses were distinct from the Southern Hemisphere vaccine strains of the corresponding season but matched with vaccines of the following season. Influenza A(H3N2) strains from Myanmar belonged to clade 2a.3 and shared the highest genetic proximity with Bahraini strains. B/Victoria viruses belonged to clade V1A.3a.2 and were genetically similar to Bangladeshi strains. This study highlights the importance of performing influenza virus surveillance with genetic characterization of the influenza virus in Myanmar, to contribute to global influenza surveillance during the COVID-19 pandemic.

    DOI： 10.3390/v15020583

    PubMed

    researchmap

  • Establishment of a Cell Culture Model Permissive for Infection by Hepatitis B and C Viruses 査読

    Teruhime Otoguro, Tomohisa Tanaka, Hirotake Kasai, Nobuhiro Kobayashi, Atsuya Yamashita, Takasuke Fukuhara, Akihide Ryo, Moto Fukai, Akinobu Taketomi, Yoshiharu Matsuura, Kohji Moriishi

    Hepatology Communications   5 ( 4 )   634 - 649   2021年4月

    　詳細を見る

    担当区分：筆頭著者   掲載種別：研究論文（学術雑誌）   出版者・発行元：Wiley  

    Compared with each monoinfection, coinfection with hepatitis B virus (HBV) and hepatitis C virus (HCV) is well known to increase the risks of developing liver cirrhosis and hepatocellular carcinoma. However, the mechanism by which HBV/HCV coinfection is established in hepatocytes is not well understood. Common cell culture models for coinfection are required to examine viral propagation. In this study, we aimed to establish a cell line permissive for both HBV and HCV infection. We first prepared a HepG2 cell line expressing sodium taurocholate cotransporting polypeptide, an HBV receptor, and then selected a cell line highly permissive for HBV infection, G2/NT18-B. After transduction with a lentivirus-encoding microRNA-122, the cell line harboring the highest level of replicon RNA was selected and then treated with anti-HCV compounds to eliminate the replicon RNA. The resulting cured cell line was transduced with a plasmid-encoding CD81. The cell line permissive for HCV infection was cloned and then designated the G2BC-C2 cell line, which exhibited permissiveness for HBV and HCV propagation. JAK inhibitor I potentiated the HCV superinfection of HBV-infected cells, and fluorescence-activated cell-sorting analysis indicated that HBV/HCV double-positive cells accounted for approximately 30% of the coinfected cells. Among several host genes tested, cyclooxygenase-2 showed synergistic induction by coinfection compared with each monoinfection. Conclusion: These data indicate that our in vitro HBV/HCV coinfection system provides an easy-to-use platform for the study of host and viral responses against coinfection and the development of antiviral agents targeting HBV and HCV.

    DOI： 10.1002/hep4.1653

    Scopus

    researchmap

    その他リンク： https://onlinelibrary.wiley.com/doi/full-xml/10.1002/hep4.1653

  • Roles of the 5' Untranslated Region of Nonprimate Hepacivirus in Translation Initiation and Viral Replication. 国際誌

    Tomohisa Tanaka, Teruhime Otoguro, Atsuya Yamashita, Hirotake Kasai, Takasuke Fukuhara, Yoshiharu Matsuura, Kohji Moriishi

    Journal of virology   92 ( 7 )   2018年4月

    　詳細を見る

    記述言語：英語   掲載種別：研究論文（学術雑誌）  

    The 5' untranslated region (UTR) of hepatitis C virus (HCV), which is composed of four domains (I, II, III, and IV) and a pseudoknot, is essential for translation and viral replication. Equine nonprimate hepacivirus (EHcV) harbors a 5' UTR consisting of a large 5'-terminal domain (I); three additional domains (I', II, and III), which are homologous to domains I, II, and III, respectively, of HCV; and a pseudoknot, in the order listed. In this study, we investigated the roles of the EHcV 5' UTR in translation and viral replication. The internal ribosome entry site (IRES) activity of the EHcV 5' UTR was lower than that of the HCV 5' UTR in several cell lines due to structural differences in domain III. Domains I and III of EHcV were functional in the HCV 5' UTR in terms of IRES activity and the replication of the subgenomic replicon (SGR), although domain II was not exchangeable between EHcV and HCV for SGR replication. Furthermore, the region spanning domains I and I' of EHcV (the 5'-proximal EHcV-specific region) improved RNA stability and provided the HCV SGR with microRNA 122 (miR-122)-independent replication capability, while EHcV domain I alone improved SGR replication and RNA stability irrespective of miR-122. These data suggest that the region spanning EHcV domains I and I' improves RNA stability and viral replication regardless of miR-122 expression. The 5'-proximal EHcV-specific region may represent an inherent mechanism to facilitate viral replication in nonhepatic tissues.IMPORTANCE EHcV is the closest viral homolog to HCV among other hepaciviruses. HCV exhibits a narrow host range and liver-specific tropism, while epidemiological reports suggest that EHcV infects the liver and respiratory organs in horses, donkeys, and dogs. However, the mechanism explaining the differences in host or organ tropism between HCV and EHcV is unknown. In this study, our data suggest that the 5' untranslated region (UTR) of EHcV is composed of an internal ribosome entry site (IRES) element that is functionally exchangeable with HCV IRES elements. Furthermore, the 5'-proximal EHcV-specific region enhances viral replication and RNA stability in a miR-122-independent manner. Our data suggest that the region upstream of domain II in the EHcV 5' UTR contributes to the differences in tissue tropism observed between these hepaciviruses.

    DOI： 10.1128/JVI.01997-17

    PubMed

    researchmap

  • Inhibitory effects of metachromin A on hepatitis B virus production via impairment of the viral promoter activity. 国際誌

    Atsuya Yamashita, Mayumi Tamaki, Hirotake Kasai, Tomohisa Tanaka, Teruhime Otoguro, Akihide Ryo, Shinya Maekawa, Nobuyuki Enomoto, Nicole J de Voogd, Junichi Tanaka, Kohji Moriishi

    Antiviral research   145   136 - 145   2017年9月

    　詳細を見る

    記述言語：英語   掲載種別：研究論文（学術雑誌）  

    The currently available antiviral agents for chronic infection with hepatitis B virus (HBV) are pegylated interferon-α and nucleoside/nucleotide analogues, although it has been difficult to completely eliminate covalently closed circular DNA (cccDNA) from patients. To identify an antiviral compound targeting HBV core promoter, 15 terpenes originating from marine organisms were screened using a cell line expressing firefly luciferase under the control of the HBV core promoter. Metachromin A, which is a merosesquiterpene isolated from the marine sponge Dactylospongia metachromia, inhibited the viral promoter activity at the highest level among the tested compounds, and suppressed HBV production with an EC50 value of 0.8 μM regardless of interferon signaling and cytotoxicity. The analysis on the structure-activity relationship revealed that the hydroquinone moiety, and the double bonds at carbon numbers-5 and -9 in metachromin A are crucial for anti-HBV activity. Furthermore, metachromin A reduced the protein level but not the RNA level of hepatic nuclear factor 4α, which mainly upregulates the activities of enhancer I/X promoter and enhancer II/core promoter. These results suggest that metachromin A can inhibit HBV production via impairment of the viral promoter activity. Antiviral agents targeting the viral promoter may ameliorate HBV-related disorders regardless of remaining cccDNA.

    DOI： 10.1016/j.antiviral.2017.08.001

    PubMed

    researchmap

  • Cinnamic acid derivatives inhibit hepatitis C virus replication via the induction of oxidative stress. 国際誌

    Ryota Amano, Atsuya Yamashita, Hirotake Kasai, Tomoka Hori, Sayoko Miyasato, Setsu Saito, Hiromasa Yokoe, Kazunori Takahashi, Tomohisa Tanaka, Teruhime Otoguro, Shinya Maekawa, Nobuyuki Enomoto, Masayoshi Tsubuki, Kohji Moriishi

    Antiviral research   145   123 - 130   2017年9月

    　詳細を見る

    記述言語：英語   掲載種別：研究論文（学術雑誌）  

    Several cinnamic acid derivatives have been reported to exhibit antiviral activity. In this study, we prepared 17 synthetic cinnamic acid derivatives and screened them to identify an effective antiviral compound against hepatitis C virus (HCV). Compound 6, one of two hit compounds, suppressed the viral replications of genotypes 1b, 2a, 3a, and 4a with EC50 values of 1.5-8.1 μM and SI values of 16.2-94.2. The effect of compound 6 on the phosphorylation of Tyr705 in signal transducer and activator of transcription 3 (STAT3) was investigated because a cinnamic acid derivative AG490 was reported to suppress HCV replication and the activity of Janus kinase (JAK) 2. Compound 6 potently suppressed HCV replication, but it did not inhibit the JAK1/2-dependent phosphorylation of STAT3 Tyr705 at the same concentration. Furthermore, a pan-JAK inhibitor tofacitinib potently impaired phosphorylation of STAT3 Tyr 705, but it did not inhibit HCV replication in the replicon cells and HCV-infected cells at the same concentration, supporting the notion that the phosphorylated state of STAT3 Tyr705 is not necessarily correlated with HCV replication. The production of reactive oxygen species (ROS) was induced by treatment with compound 6, whereas N-acetyl-cysteine restored HCV replication and impaired ROS production in the replicon cells treated with compound 6. These data suggest that compound 6 inhibits HCV replication via the induction of oxidative stress.

    DOI： 10.1016/j.antiviral.2017.07.018

    PubMed

    researchmap

  • Hepatitis B virus prevents excessive viral production via reduction of cell death-inducing DFF45-like effectors. 国際誌

    Jun Yasumoto, Hirotake Kasai, Kentaro Yoshimura, Teruhime Otoguro, Koichi Watashi, Takaji Wakita, Atsuya Yamashita, Tomohisa Tanaka, Sen Takeda, Kohji Moriishi

    The Journal of general virology   98 ( 7 )   1762 - 1773   2017年7月

    　詳細を見る

    記述言語：英語   掲載種別：研究論文（学術雑誌）  

    The relationship between hepatitis B virus (HBV) infection and lipid accumulation remains largely unknown. In this study, we investigated the effect of HBV propagation on lipid droplet growth in HBV-infected cells and HBV-producing cell lines, HepG2.2.15 and HBV-inducible Hep38.7-Tet. The amount of intracellular triglycerides was significantly reduced in HBV-infected and HBV-producing cells compared with HBV-lacking control cells. Electron and immunofluorescent microscopic analyses showed that the average size of a single lipid droplet (LD) was significantly less in the HBV-infected and HBV-producing cells than in the HBV-lacking control cells. Cell death-inducing DFF45-like effectors (CIDEs) B and C (CIDEB and CIDEC), which are involved in LD expansion for the improvement of lipid storage, were expressed at a significantly lower level in HBV-infected or HBV-producing cells than in HBV-lacking control cells, while CIDEA was not detected in those cells regardless of HBV production. The activity of the CIDEB and CIDEC gene promoters was impaired in HBV-infected or HBV-producing cells compared to HBV-lacking control cells, while CIDEs potentiated HBV core promoter activity. The amount of HNF4α, that can promote the transcription of CIDEB was significantly lower in HBV-producing cells than in HBV-lacking control cells. Knockout of CIDEB or CIDEC significantly reduced the amount of supernatant HBV DNA, intracellular viral RNA and nucleocapsid-associated viral DNA, while the expression of CIDEB or CIDEC recovered HBV production in CIDEB- or CIDEC-knockout cells. These results suggest that HBV regulates its own viral replication via CIDEB and CIDEC.

    DOI： 10.1099/jgv.0.000813

    PubMed

    researchmap

  • Inhibitory effect of presenilin inhibitor LY411575 on maturation of hepatitis C virus core protein, production of the viral particle and expression of host proteins involved in pathogenicity. 国際誌

    Teruhime Otoguro, Tomohisa Tanaka, Hirotake Kasai, Atsuya Yamashita, Kohji Moriishi

    Microbiology and immunology   60 ( 11 )   740 - 753   2016年11月

    　詳細を見る

    記述言語：英語   掲載種別：研究論文（学術雑誌）  

    Hepatitis C virus (HCV) core protein is responsible for the formation of infectious viral particles and induction of pathogenicity. The C-terminal transmembrane region of the immature core protein is cleaved by signal peptide peptidase (SPP) for maturation of the core protein. SPP belongs to the family of presenilin-like aspartic proteases. Some presenilin inhibitors are expected to suppress HCV infection and production; however, this anti-HCV effect has not been investigated in detail. In this study, presenilin inhibitors were screened to identify anti-HCV compounds. Of the 13 presenilin inhibitors tested, LY411575 was the most potent inhibitor of SPP-dependent cleavage of HCV core protein. Production of intracellular core protein and supernatant infectious viral particles from HCV-infected cells was significantly impaired by LY411575 in a dose-dependent manner (half maximum inhibitory concentration = 0.27 μM, cytotoxic concentration of the extracts to cause death to 50% of viable cells > 10 μM). No effect of LY411575 on intracellular HCV RNA in the subgenomic replicon cells was detected. LY411575 synergistically promoted daclatasvir-dependent inhibition of viral production, but not that of viral replication. Furthermore, LY411575 inhibited HCV-related production of reactive oxygen species and expression of NADPH oxidases and vascular endothelial growth factor. Taken together, our data suggest that LY411575 suppresses HCV propagation through SPP inhibition and impairs host gene expressions related to HCV pathogenicity.

    DOI： 10.1111/1348-0421.12448

    PubMed

    researchmap

▶ 全件表示

MISC

  • COVID-19流行下における呼吸器感染症の流行ダイナミクス変化

    乙黒 光姫, 我妻 奎太

    国際保健医療   39 ( 1 )   15 - 17   2024年

    　詳細を見る

    記述言語：日本語   出版者・発行元：日本国際保健医療学会  

    DOI： 10.11197/jaih.39.15

    researchmap