研究者基本情報

• 博士（医学）, 北海道大学, 1994年03月

• https://researchmap.jp/read0180096

• 200901041582949278

• 獣医病理学
• ウマヘルペスウイルス
• ウイルス性脳炎
• 鼻疽

• ライフサイエンス, 獣医学
• ライフサイエンス, ウイルス学

• 学士課程, 獣医学部
• 博士課程, 獣医学院

研究活動情報

• Lysine lactylation regulates ATF4-mediated stress responses under glucose starvation in canine hemangiosarcoma
  Tamami Suzuki; Kazuki Heishima; Jumpei Yamazaki; Masaya Yamazaki; Ryohei Kinoshita; Sangho Kim; Kenji Hosoya; Yuko Okamatsu-Ogura; Michihito Sasaki; Peng Xu; Takashi Kimura; Qin Yan; Keisuke Aoshima
  Cold Spring Harbor Laboratory, 2025年08月13日
  Hemangiosarcoma (HSA) is a malignant endothelial tumor that occurs frequently in dogs but is rare in other species including humans. Due to its aggressive behavior and limited therapeutic options, patient prognosis is generally poor. Tumor cells produce excess lactate via anerobic glycolysis, and it regulate gene expressions through histone lactylation in response to cellular metabolic conditions. However, how histone lactylation affects biological behavior under glucose-limited conditions in HSA remains unknown. Here, we established canine HSA cell lines and patient-derived xenograft models and investigated the role of histone lactylation during glucose deprivation. HSA cells exhibited higher global histone lactylation levels than normal endothelial cells. Although glucose restriction reduced global histone lactylation levels, Cleavage Under Targets and Tagmentation (CUT&Tag) analysis revealed enrichment of lactylation peaks at transcription‑start sites (TSSs) of ATF4‑regulated stress‑response, asparagine biosynthesis and immune‑related genes. TSSs of stress-response genes were co-occupied with RNA polymerase II phosphorylated at serine 5 and showed increased gene expressions, suggesting that lactylation at TSSs activated transcription under glucose-deprived conditions. [U-13C]glutamine tracing indicated that HSA cells synthesized asparagine from glutamine when glucose was scarce. Asparagine supplementation modestly activated cell proliferation. In HSA patient tissues, H3K18la levels were heterogeneous, and M2-like macrophages preferentially infiltrated tumor regions showing low histone lactylation levels. Consistently, glucose‑starved HSA cells attracted macrophages and induced M2‑like polarization in vitro. These findings demonstrate that lysine lactylation, possibly histone lactylation, persists even under glucose-deprived conditions and regulate transcription that supports tumor cell survival and fosters a pro-tumor microenvironment.
• Calcinosis circumscripta of the extremities and the tongue with multifocal arterial calcification secondary to chronic kidney disease in a cat.
  Ai Koshikawa; Shingo Miki; Sangho Kim; Takashi Kimura; Keisuke Aoshima
  The Journal of veterinary medical science, 2025年07月18日, ［国内誌］
  英語, 研究論文（学術雑誌）, A 3-year-old neutered male mixed-breed cat was presented with right urinary tract obstruction caused by a urolith and severe atrophy of the left kidney. In the next year and a half, chronic kidney disease (CKD) progressed, and several masses were identified in the extremities, along with an ulcer on the tongue. Histologically, the extremity masses consisted of calcium deposits separated by fibrovascular septa, and the tongue ulcer showed severe neutrophilic infiltration with pervasive calcium deposition. These lesions were diagnosed as calcinosis circumscripta (CCs). Concurrently, multifocal mineralization of the aorta and of small- to medium-sized arteries in several organs indicated widespread vascular calcification. Both extremity and vascular lesions were likely secondary to the excessive calcium-phosphate product caused by CKD. Although CCs in either the extremities or tongue has been reported in cats, this case is notable for the presence of CCs in both extremities and tongue with systemic vascular calcification.
• Comparison of immunogenicity of 17 Burkholderia mallei antigens and whole cell lysate using indirect ELISA.
  Yoshiki Ichikawa; Yukiko Iinuma; Tomohiro Okagawa; Ryo Shimbo; Batchuluun Enkhtuul; Ochirbat Khurtsbaatar; Yuta Kinoshita; Hidekazu Niwa; Keisuke Aoshima; Atsushi Kobayashi; Vanaabaatar Batbaatar; Kazuhiko Ohashi; Takashi Kimura
  The Journal of veterinary medical science, 87, 4, 394, 401, 2025年04月01日, ［査読有り］, ［最終著者, 責任著者］, ［国内誌］
  英語, 研究論文（学術雑誌）, Glanders is a World Organization for Animal Health (WOAH)-notifiable equine disease caused by the infection of Burkholderia mallei, and is endemic in Mongolia, South Asia, Africa, and South America. While the complement fixation test (CFT) has been widely used for serodiagnosis of glanders and is considered a standard serological test, it has several limitations. These limitations include poor specificity, labor intensive techniques, variability in antigen and protocol. Consequently, indirect enzyme-linked immunosorbent assays (iELISAs) based on recombinant proteins have been developed as alternative serodiagnostic assays to address some of the challenges associated with the CFT. The accuracy of iELISA relies on the B. mallei proteins used as an antigen. Hence, to determine the best diagnostic candidate in iELISA, in terms of sensitivity and specificity, a comparison of 17 immunogenic B. mallei proteins and detergent-based whole cell lysate (WCL) was performed. According to the sensitivity and specificity on the sera from glanderous and non-glanderous Mongolian native horses, iELISA using Hcp1, GroEL, and detergent-based WCL represented the highest diagnostic accuracy. These three candidates did not have cross-reactivity to horse sera with several other equine diseases. WCL, Hcp1, and GroEL showed considerable potential as antigens for iELISA in the serodiagnosis of glanders in Mongolia. Detergent-based WCL extraction offers a consistent approach for the preparation of reliable B. mallei antigen. WCL-iELISA should be further validated in a large-scale study to meet WOAH demands.
• A novel ready-to-use loop-mediated isothermal amplification (LAMP) method for detection of Burkholderia mallei and B. pseudomallei.
  Mitsuru Nakase; Jeewan Thapa; Vanaabaatar Batbaatar; Ochirbat Khurtsbaatar; Batchuluun Enkhtuul; Jugderkhorloo Unenbat; Baasansuren Lkham; Sachiho Fujita; Ai Koshikawa; Apichai Tuanyok; Vannarat Saechan; Hideaki Higashi; Kyoko Hayashida; Yasuhiko Suzuki; Chie Nakajima; Takashi Kimura
  BMC microbiology, 25, 1, 36, 36, 2025年01月21日, ［査読有り］, ［最終著者, 責任著者］, ［国際誌］
  英語, 研究論文（学術雑誌）, BACKGROUND: Glanders and melioidosis are contagious zoonotic diseases caused by Burkholderia mallei and B. pseudomallei, respectively. Bacterial isolation and polymerase chain reaction (PCR) have been used to detect these bacteria in animals suspected of infection; however, both methods require skilled experimental techniques and expensive equipment. These obstacles make it difficult to diagnose B. mallei and B. pseudomallei infections in areas where reagents and equipment are difficult to procure. To solve this problem, we developed an easy and ready-to-use dried-format diagnostic tool based on loop-mediated isothermal amplification (LAMP) method. RESULTS: The primer set targeting the internal transcribed spacer (ITS) region detected 10 genomic copies of B. mallei DNA and B. pseudomallei DNA using the conventional liquid LAMP method. This primer set did not detect any other Burkholderia species. Using this novel primer set, a dried-format in-house LAMP method with high sensitivity and specificity was developed. This method was used to test for the presence of B. mallei DNA in swabs collected from the nasal cavity and ulcerated skin of 19 B. mallei-infected horses and five uninfected horses and was compared with the real-time PCR method. These two tests showed 87.5% agreement for the positive samples and 100% agreement for the negative samples. This method detected all tested B. pseudomallei clinical isolates. CONCLUSIONS: We established the first dry LAMP method for the detection of B. mallei and B. pseudomallei. This study provided a simple, rapid, cost-effective, and sensitive diagnostic tool for glanders and melioidosis.
• Nodal T-cell lymphoma with eosinophilic infiltration and sclerosing fibroplasia in a cat with eosinophilia.
  Tamami Suzuki; Jumpei Yamazaki; Kouta Yamaguchi; Keisuke Aoshima; Takashi Kimura
  The Journal of veterinary medical science, 86, 12, 1252, 1255, 2024年12月01日, ［査読有り］, ［最終著者, 責任著者］, ［国内誌］
  英語, 研究論文（学術雑誌）, An 8-year-old castrated male mixed-breed cat presented with an abdominal mass of unknown origin, accompanied by eosinophilia. Autopsy revealed mild-to-severe enlargement of lymph nodes throughout the body and multiple nodules in the lungs. Histopathologically, the lymph nodes showed severe fibroplasia and infiltration by a large number of eosinophils and fewer tumor cells, exhibiting large-sized lymphoid cell morphology. Metastatic lesions of tumor cells with eosinophilic infiltration and fibrosis were observed in the lungs, liver, kidneys, stomach, and intestines. Immunohistochemistry revealed that the tumor cells were positive for CD3 and negative for B cell and mast cell markers. Thus, T-cell lymphoma with eosinophilic infiltration and sclerosing fibroplasia was diagnosed.
• Characterization of a mammalian orthoreovirus isolated from the large flying fox, Pteropus vampyrus, in Indonesia.
  Kittiya Intaruck; Koshiro Tabata; Yukari Itakura; Nijiho Kawaguchi; Mai Kishimoto; Agus Setiyono; Ekowati Handharyani; Hayato Harima; Takashi Kimura; William W Hall; Yasuko Orba; Hirofumi Sawa; Michihito Sasaki
  The Journal of general virology, 105, 9, 2024年09月, ［国際誌］
  英語, 研究論文（学術雑誌）, Fruit bats serve as an important reservoir for many zoonotic pathogens, including Nipah virus, Hendra virus, Marburg virus and Lyssavirus. To gain a deeper insight into the virological characteristics, pathogenicity and zoonotic potential of bat-borne viruses, recovery of infectious viruses from field samples is important. Here, we report the isolation and characterization of a mammalian orthoreovirus (MRV) from a large flying fox (Pteropus vampyrus) in Indonesia, which is the first detection of MRV in Southeast Asia. MRV was recovered from faecal samples of three different P. vampyrus in Central Java. Nucleotide sequence analysis revealed that the genome of the three MRV isolates shared more than 99% nucleotide sequence identity. We tentatively named one isolated strain as MRV12-52 for further analysis and characterization. Among 10 genome segments, MRV12-52 S1 and S4, which encode the cell-attachment protein and outer capsid protein, had 93.6 and 95.1% nucleotide sequence identities with known MRV strains, respectively. Meanwhile, the remaining genome segments of MRV12-52 were divergent with 72.9-80.7 % nucleotide sequence identities. Based on the nucleotide sequence of the S1 segment, MRV12-52 was grouped into serotype 2, and phylogenetic analysis demonstrated evidence of past reassortment events. In vitro characterization of MRV12-52 showed that the virus efficiently replicated in BHK-21, HEK293T and A549 cells. In addition, experimental infection of laboratory mice with MRV12-52 caused severe pneumonia with 75% mortality. This study highlights the presence of pathogenic MRV in Indonesia, which could serve as a potential animal and public health concern.
• First molecular characterization of Burkholderia mallei strains isolated from horses in Mongolia
  Yoshiki Ichikawa; Liushiqi Borjigin; Batchuluun Enkhtuul; Ochirbat Khurtsbaatar; Keisuke Aoshima; Atsushi Kobayashi; Vanaabaatar Batbaatar; Takashi Kimura
  Infection, Genetics and Evolution, 123, 105616, 105616, Elsevier BV, 2024年09月, ［査読有り］, ［最終著者, 責任著者］, ［国際誌］
  英語, 研究論文（学術雑誌）, Glanders, a highly contagious and often fatal disease affecting equids, is caused by Burkholderia mallei. Although sporadic cases of equine glanders have recently been documented in Mongolia, genome sequencing and molecular studies of the bacteria within this region are lacking. This study provided the first molecular characterization of B. mallei isolated from four native Mongolian horses from two different provinces in 2019 and 2022 by applying whole-genome sequencing with two SNP types (previously developed genotyping with 15 SNP markers that provide global coverage of the B. mallei population and the core genome coding SNP typing developed in this study). The Mongolian isolates were located within the L3B1 cluster, which was previously associated with the V-120 strain from Russia. Within the L3B1 cluster shared by neighboring countries, they were in a unique subbranch. In this study, specific SNP markers unique to the Mongolian strains were identified to track these strains using a high-resolution melting analysis (HRMA). This study revealed the unique phylogenetic background of Mongolian strains isolated from the eastern part of Mongolia. HRMA specific to the Mongolian subbranch may contribute to the molecular epidemiological monitoring of glanders in Mongolia and surrounding countries.
• Identification of the Promoter Antisense Transcript Enhancing the Transcription of the Equine Herpesvirus-1 Immediate-Early Gene.
  Mayuko Maeda; Miou Abe; Keisuke Aoshima; Atsushi Kobayashi; Hideto Fukushi; Takashi Kimura
  Viruses, 16, 8, 2024年07月25日, ［査読有り］, ［最終著者, 責任著者］, ［国際誌］
  英語, 研究論文（学術雑誌）, Equine herpesvirus-1 (EHV-1) causes respiratory diseases, abortion, and encephalomyelitis in horses. The EHV-1 immediate-early (IE) protein, essential for viral replication, is transactivated by the binding of a multiprotein complex including the open reading frame 12 (ORF12) and some host factors to the IE promoter region. Promoter-associated non-coding RNAs (pancRNAs), which are transcribed from bidirectional promoters, regulate the transcription of neighboring genes in mammals and pathogens. In this study, we identified a novel pancRNA transcribed from across the areas of the 5'-untranslated region and a promoter of EHV-1 IE and named it IE pancRNA. IE pancRNA and mRNA were simultaneously expressed in EHV-1-infected RN33B-A68B2M cells. This pancRNA was also transcribed in RK13 and E. Derm cells, which are highly susceptible to EHV-1 infection. Furthermore, IE pancRNA upregulated IE gene expression in the presence of ORF12, and stable expression of IE pancRNA increased the number of EHV-1-infected RN33B-A68B2M cells. These results suggest that IE pancRNAs facilitate EHV-1 proliferation by promoting IE gene expression.
• FOUR-WEEK ORAL ADMINISTRATION OF BALOXAVIR MARBOXIL AS AN ANTI-INFLUENZA VIRUS DRUG SHOWS NO TOXICITY IN CHICKENS
  Miki M; Obara RD; Nishimura K; Shishido T; Ikenaka Y; Oka R; Sato K; Nakayama SMM; Kimura T; Kobayashi A; Aoshima K; Saito K; Hiono T; Isoda N; Sakoda Y
  J Zoo Wildl Med, 55, 2, 313, 321, 2024年06月, ［査読有り］
  英語, 研究論文（学術雑誌）
• A point mutation in GPI-attachment signal peptide accelerates the development of prion disease
  Kobayashi A; Hirata T; Shimazaki T; Munesue Y; Aoshima K; Kimura T; Nio-Kobayashi J; Hasebe R; Takeuchi A; Matsuura Y; Kusumi S; Koga D; Iwasaki Y; Kinoshita T; Mohri S; Kitamoto T
  Acta Neuropathol, 145, 5, 637, 650, 2023年03月, ［査読有り］, ［国際誌］
  英語, 研究論文（学術雑誌）, A missense variant from methionine to arginine at codon 232 (M232R) of the prion protein gene accounts for ~ 15% of Japanese patients with genetic prion diseases. However, pathogenic roles of the M232R substitution for the induction of prion disease have remained elusive because family history is usually absent in patients with M232R. In addition, the clinicopathologic phenotypes of patients with M232R are indistinguishable from those of sporadic Creutzfeldt-Jakob disease patients. Furthermore, the M232R substitution is located in the glycosylphosphatidylinositol (GPI)-attachment signal peptide that is cleaved off during the maturation of prion proteins. Therefore, there has been an argument that the M232R substitution might be an uncommon polymorphism rather than a pathogenic mutation. To unveil the role of the M232R substitution in the GPI-attachment signal peptide of prion protein in the pathogenesis of prion disease, here we generated a mouse model expressing human prion proteins with M232R and investigated the susceptibility to prion disease. The M232R substitution accelerates the development of prion disease in a prion strain-dependent manner, without affecting prion strain-specific histopathologic and biochemical features. The M232R substitution did not alter the attachment of GPI nor GPI-attachment site. Instead, the substitution altered endoplasmic reticulum translocation pathway of prion proteins by reducing the hydrophobicity of the GPI-attachment signal peptide, resulting in the reduction of N-linked glycosylation and GPI glycosylation of prion proteins. To the best of our knowledge, this is the first time to show a direct relationship between a point mutation in the GPI-attachment signal peptide and the development of disease.
• Virological, pathological, and glycovirological investigations of an Ezo red fox and a tanuki naturally infected with H5N1 highly pathogenic avian influenza viruses in Hokkaido, Japan
  Takahiro Hiono; Daiki Kobayashi; Atsushi Kobayashi; Tamami Suzuki; Yuki Satake; Rio Harada; Keita Matsuno; Mariko Sashika; Hinako Ban; Maya Kobayashi; Keisuke Aoshima; Fumihito Takaya; Hiroko Fujita; Norikazu Isoda; Takashi Kimura; Yoshihiro Sakoda
  Virology, 578, 35, 44, 2023年01月, ［査読有り］
  英語, 研究論文（学術雑誌）
• Detection of Changes in Monoamine Neurotransmitters by the Neonicotinoid Pesticide Imidacloprid Using Mass Spectrometry.
  Anri Hirai; Ryo Yamazaki; Atsushi Kobayashi; Takashi Kimura; Kei Nomiyama; Shuichi Shimma; Shouta M M Nakayama; Mayumi Ishizuka; Yoshinori Ikenaka
  Toxics, 10, 11, 2022年11月17日, ［国際誌］
  英語, 研究論文（学術雑誌）, Monoamine neurotransmitters (MAs), including dopamine (DA) and serotonin (5-HT), regulate brain functions such as behavior, memory, and learning. Neonicotinoids are pesticides that are being used more frequently. Neonicotinoid exposure has been observed to produce neurological symptoms, such as altered spontaneous movements and anxiety-like behaviors, which are suspected to be caused by altered MA levels. However, current neurotoxicity tests are not sufficiently sensitive enough to make these determinations. In this study, we performed some behavior tests, and derivatization reagents to improve the ionization efficiency, which was applied to liquid chromatography mass spectrometry (LC-MS/MS) to reveal the effect of neonicotinoid administration on MAs in the brain. We orally administered the neonicotinoid imidacloprid (0, 10, and 50 mg/kg body weight) to C57BL/6NCrSlc mice. In the behavior tests, a decrease in activity was observed. The LC-MS/MS quantification of MAs in various brain regions showed a decrease in some MA levels in the olfactory bulb and the striatum. These results showed, for the first time, that even a low dose of imidacloprid could alter MA levels in various parts of the brain.
• Isolation and characterization of an orthoreovirus from Indonesian fruit bats.
  Kittiya Intaruck; Yukari Itakura; Mai Kishimoto; Herman M Chambaro; Agus Setiyono; Ekowati Handharyani; Kentaro Uemura; Hayato Harima; Satoshi Taniguchi; Masayuki Saijo; Takashi Kimura; Yasuko Orba; Hirofumi Sawa; Michihito Sasaki
  Virology, 575, 10, 19, 2022年10月, ［国際誌］
  英語, 研究論文（学術雑誌）, Nelson Bay orthoreovirus (NBV) is an emerging bat-borne virus and causes respiratory tract infections in humans sporadically. Over the last two decades, several strains genetically related to NBV were isolated from humans and various bat species, predominantly in Southeast Asia (SEA), suggesting a high prevalence of the NBV species in this region. In this study, an orthoreovirus (ORV) belonging to the NBV species was isolated from Indonesian fruit bats' feces, tentatively named Paguyaman orthoreovirus (PgORV). Serological studies revealed that 81.2% (108/133) of Indonesian fruit bats sera had neutralizing antibodies against PgORV. Whole-genome sequencing and phylogenetic analysis of PgORV suggested the occurrence of past reassortments with other NBV strains isolated in SEA, indicating the dispersal and circulation of NBV species among bats in this region. Intranasal PgORV inoculation of laboratory mice caused severe pneumonia. Our study characterized PgORV's unique genetic background and highlighted the potential risk of PgORV-related diseases in Indonesia.
• 鼻疽の診断抗原の探索
  市川 世識; 飯沼 由希帆; 岡川 朋弘; 前川 直也; 村田 史郎; 今内 覚; 木下 優太; 丹羽 秀和; 青島 圭佑; 小林 篤史; 大橋 和彦; 木村 享史
  日本獣医学会学術集会講演要旨集, 165回, [DI1A, 09], (公社)日本獣医学会, 2022年09月
  日本語
• 鼻疽の診断抗原の探索
  市川 世識; 飯沼 由希帆; 岡川 朋弘; 前川 直也; 村田 史郎; 今内 覚; 木下 優太; 丹羽 秀和; 青島 圭佑; 小林 篤史; 大橋 和彦; 木村 享史
  日本獣医学会学術集会講演要旨集, 165回, [DI1A, 09], (公社)日本獣医学会, 2022年09月
  日本語
• Behavior and toxic effects of Pb in a waterfowl model with oral exposure to Pb shots: Investigating Pb exposure in wild birds.
  Hiroshi Sato; Chihiro Ishii; Shouta M M Nakayama; Takahiro Ichise; Keisuke Saito; Yukiko Watanabe; Kohei Ogasawara; Ryota Torimoto; Atsushi Kobayashi; Takashi Kimura; Yukiko Nakamura; Junya Yamagishi; Yoshinori Ikenaka; Mayumi Ishizuka
  Environmental pollution (Barking, Essex : 1987), 119580, 119580, 2022年06月06日, ［国際誌］
  英語, 研究論文（学術雑誌）, Among wild birds, lead (Pb) exposure caused by ingestion of ammunition is a worldwide problem. We aimed to reveal the behavior and toxic effect of Pb caused by ingesting Pb shots in waterfowl. Four male, eight-week old Muscovy ducks (Cairina moschata) were given three Pb shots (approximately 240 mg in total) orally and then fed for 29 days after exposure, simulating a low-dose Pb exposure in wild waterfowl. During the breeding period, blood samples were collected 10 times, and fecal samples every day. Additionally, 22 fresh tissue and 6 bone samples were obtained from each duck through the dissection. Although there were no gross abnormalities, the maximum blood Pb concentration of each duck ranged from 0.6 to 3.7 mg/L, reaching a threshold concentration indicative of clinical symptoms (>0.5 mg/L). δ-aminolevulinic acid dehydratase declined one day after exposure and remained low throughout the feeding period. Hematocrit also tended to decrease, indicating signs of anemia. The highest Pb accumulation was observed in the bones, followed by the kidneys, intestinal tracts, and liver. High Pb accumulation in the bones, which are known to have a long Pb half-life, suggested that Pb would remain in the body and possibly affect bird health beyond 28 days after exposure. Gene expression analysis showed a significant increase in the expression of the toll-like receptor-3 gene, which is involved in virus discrimination in the liver, suggesting a disruption of the immune system. Microbiota analyses showed a correlation between the blood Pb concentration and the abundances of Lachnospiraceae and Ruminococcaceae, suggesting that Pb affects lipid metabolism. These results provide fundamental data on Pb exposure in wild birds and a new perspective on the damage such exposure causes.
• The expression of histone lysine demethylase 2B in canine hemangiosarcoma is associated with disease progression
  Kevin Christian; M. Gulay; Keisuke Aoshima; Atsushi Kobayashi; Takashi Kimura
  Veterinary and Comparative Oncology, 20, 2, 529, 534, 2022年06月, ［査読有り］
  英語, 研究論文（学術雑誌）
• Manipulating Histone Acetylation Leads to Antitumor Effects in Hemangiosarcoma Cells.
  Tamami Suzuki; Keisuke Aoshima; Jumpei Yamazaki; Atsushi Kobayashi; Takashi Kimura
  Veterinary and comparative oncology, 2022年05月14日, ［国際誌］
  英語, 研究論文（学術雑誌）, Canine hemangiosarcoma (HSA) is a malignant tumor derived from endothelial cells. No effective treatment has yet been developed because of the lack of understanding of its pathogenesis. Histone acetylation, an epigenetic modification, is highly associated with cancer pathogenesis. Manipulating histone acetylation by histone deacetylase inhibitors (HDACi) or bromodomain and extraterminal domain inhibitors (BETi) is one approach to treat various cancers. However, the role of histone acetylation in HSA remains unknown. This study aimed to investigate how histone acetylation functions in HSA pathogenesis using two HDACi, suberanilohydroxamic acid (SAHA) and valproic acid (VPA), and one BETi, JQ1, in vitro and in vivo. Histone acetylation levels were high in cell lines and heterogeneous in clinical cases. SAHA and JQ1 induced apoptosis in HSA cell lines. HSA cell lines treated with SAHA and VPA upregulated inflammatory-related genes and attracted macrophage cell line RAW264 cells, which suggests that SAHA and VPA can affect immune responses. JQ1 stimulated autophagy and inhibited the cell cycle in HSA cell lines. Finally, we demonstrated that JQ1 suppressed HSA tumor cell proliferation in vivo although SAHA and VPA did not affect tumor growth. These results suggest that BETi can be alternative drugs for HSA treatment. Although further research is required, our study indicated that dysregulation of histone acetylation is likely to be involved in HSA malignancy. This article is protected by copyright. All rights reserved.
• Malignant oligoastrocytoma in the spinal cord of a cat
  Dai HASEGAWA; Keisuke AOSHIMA; Kazuyoshi SASAOKA; Atsushi KOBAYASHI; Mitsuyoshi TAKIGUCHI; Takashi KIMURA
  Journal of Veterinary Medical Science, 84, 9, 1277, 1282, Japanese Society of Veterinary Science, 2022年
  研究論文（学術雑誌）
• Manipulating Histone Acetylation Leads to Adverse Effects in Hemangiosarcoma Cells
  Tamami Suzuki; Keisuke Aoshima*; Jumpei Yamazaki; Atsushi Kobayashi; Takashi Kimura; *Corresponding author
  bioRxiv, 2021年12月11日
• Potential for transmission of sporadic Creutzfeldt–Jakob disease through peripheral routes
  Atsushi Kobayashi; Yoshiko Munesue; Taishi Shimazaki; Keisuke Aoshima; Takashi Kimura; Shirou Mohri; Tetsuyuki Kitamoto
  Laboratory Investigation, 101, 10, 1327, 1330, Springer Science and Business Media LLC, 2021年10月, ［査読有り］, ［国際誌］
  英語, 研究論文（学術雑誌）, Five sporadic Creutzfeldt-Jakob disease (CJD) strains have been identified to date, based on differences in clinicopathological features of the patients, the biochemical properties of abnormal prion proteins, and transmission properties. Recent advances in our knowledge about iatrogenic transmission of sporadic CJD have raised the possibility that the infectivity of sporadic CJD strains through peripheral routes is different from that of intracranial infection. To test this possibility, here we assessed systematically the infectivity of sporadic CJD strains through the peripheral route for the first time using a mouse model expressing human prion protein. Although the infectivity of the V2 and M1 sporadic CJD strains is almost the same in intracerebral transmission studies, the V2 strain infected more efficiently than the M1 strain through the peripheral route. The other sporadic CJD strains examined lacked infectivity. Of note, both the V2 and M1 strains showed preference for mice with the valine homozygosity at the PRNP polymorphic codon. These results indicate that the V2 strain is the most infectious sporadic CJD strain for infection through peripheral routes. In addition, these findings raise the possibility that individuals with the valine homozygosity at the PRNP polymorphic codon might have higher risks of infection through peripheral routes compared with the methionine homozygotes. Thus, preventive measures against the transmission of the V2 sporadic CJD strain will be important for the eradication of iatrogenic CJD transmission through peripheral routes.
• Duck Tembusu virus induces stronger cellular responses than Japanese encephalitis virus in primary duck neurons and fibroblasts
  Sittinee Kulprasertsri; Shintaro Kobayashi; Keisuke Aoshima; Atsushi Kobayashi; Takashi Kimura
  Microbiology and Immunology, 65, 11, 481, 491, Wiley, 2021年09月08日, ［査読有り］, ［最終著者, 責任著者］, ［国際誌］
  英語, 研究論文（学術雑誌）, Duck Tembusu virus (DTMUV) and Japanese encephalitis virus (JEV) are mosquito-borne flaviviruses. These two viruses infect ducks; however, they show different neurological outcomes. The mechanism of DTMUV- and JEV-induced neuronal death has not been well investigated. In the present study, we examined the differences in the mechanisms involved in virus-induced cell death and innate immune responses between DTMUV KPS54A61 strain and JEV JaGAr-01 strain using primary duck neurons (DN) and duck fibroblasts (CCL-141). DN and CCL-141 were permissive for the infection and replication of these two viruses, which upregulated the expression of innate immunity genes. Both DTMUV and JEV induced cell death via a caspase-3-dependent manner; however, DTMUV triggered more cell death than JEV did in both CCL-141 and DN. These findings suggest that DTMUV infection causes apoptosis in duck neurons and fibroblasts more strongly than JEV. Levels of the mRNA expression of innate immunity-related genes after DTMUV infection were generally higher than levels after JEV infection, suggesting that DTMUV-induced immune response in duck cells may exhibit toxic effect rather than protective effects. This article is protected by copyright. All rights reserved.
• Systemic mucoid degeneration of the arterial tunica intima in a young dog
  Yoshiki Ichikawa; Mizuki Heishima; Kristin Vyhnal; Keisuke Aoshima; Kazuyoshi Sasaoka; Ryohei Kinoshita; Atsushi Kobayashi; Mitsuyoshi Takiguchi; Takashi Kimura
  Journal of Veterinary Diagnostic Investigation, 34, 1, 104063872110425, 104063872110425, SAGE Publications, 2021年09月04日, ［査読有り］, ［国際誌］
  英語, 研究論文（学術雑誌）, A 27-mo-old, spayed female mixed-breed dog was presented with left forelimb pain, which progressed to full thickness necrosis of the soft tissues of multiple limbs. Clinical imaging and postmortem examination suggested multiple large arterial thromboemboli. Histologic examination of vascular lesions revealed markedly thickened tunica intima with polypoid intraluminal projections, which partially to entirely occluded the arterial lumen. The expanded tunica intima was comprised of intimal accumulation of Alcian blue–positive matrix with scattered spindle-to-satellite cells. These cells were positive for von Willebrand factor and vimentin but negative for α–smooth muscle actin, suggesting endothelial origin. Deposition of the intimal mucoid matrix was observed in the elastic and muscular arteries associated with regional ischemic changes. Mucoid emboli, likely from fragmentation of proliferative intimal tissue, were identified in smaller vessels supplied by affected arteries. Based on these findings, we diagnosed systemic mucoid degeneration of the arterial tunica intima. Such systemic arterial degeneration characterized by deposition of mucoid matrix in the tunica intima has not been reported previously in dogs, to our knowledge, and should be distinguished from thromboembolism and other degenerative vascular diseases.
• Hemangiosarcoma cells induce M2 polarization and PD-L1 expression in macrophages
  Kevin Christian M. Gulay; Keisuke Aoshima; Naoya Maekawa; Satoru Konnai; Atsushi Kobayashi; Takashi Kimura
  Cold Spring Harbor Laboratory, 2021年08月01日
  Hemangiosarcoma (HSA) is a malignant tumor derived from endothelial cells. Tumor-associated macrophages are one of the major components of tumor microenvironment and crucial for cancer development. The presence and function of macrophages in HSA have not been studied because there is no syngeneic model for HSA. In this study, we evaluated two mouse HSA cell lines and one immortalized mouse endothelial cells for their usefulness as syngeneic models for canine HSA. Our results show that the ISOS-1 cell line develops tumors with similar morphology to canine HSA. ISOS-1 cells highly express KDM2B and have similar KDM2B target expression patterns with canine HSA. Moreover, we determine that in both ISOS-1 and canine HSA tumors, macrophages are present as a major constituent of the tumor microenvironment. These macrophages are positive for CD204, an M2 macrophage marker, and express PD-L1. ISOS-1-conditioned medium can induce M2 polarization and PD-L1 expression in RAW264.7 mouse macrophage cell line. These results show that ISOS-1 can be used as a syngenic model for canine HSA and suggest that macrophages play an important role in immune evasion in HSA. Using the syngeneic mouse model for canine HSA, we can further study the role of immune cells in the pathology of HSA.
• Peliosis Hepatis with Chylous Ascites in a Dog
  Kevin Christian Montecillo Gulay; Noriyuki Nagata; Keisuke Aoshima; Nozomi Shiohara; Atsushi Kobayashi; Mitsuyoshi Takiguchi; Takashi Kimura
  Journal of Comparative Pathology, 187, 63, 67, Elsevier BV, 2021年08月, ［査読有り］, ［国際誌］
  英語, 研究論文（学術雑誌）, A 6-year-old spayed female Toy Poodle dog was referred to the Hokkaido University Veterinary Teaching Hospital for abdominal distension. Abdominocentesis yielded ascitic fluid that had a mildly increased total protein concentration and a 2.7-fold higher triglyceride concentration than plasma, and was interpreted as chylous ascites. The patient had an enlarged liver, which contained multiple, small, nodular masses and cyst-like structures. Microscopically, these lesions were multifocal dilated spaces containing lymphocytes, endothelial cells, fibrin and islands of hepatocytes. Increased α-smooth muscle actin-positive cells were observed in hepatic sinusoids. Based on these findings, we diagnosed peliosis hepatis with chylous ascites, which is likely to have been due to lymphangiectasia and disrupted hepatic sinusoids. Neither Bartonella spp DNA nor mutations in ACVRL1 and MTM1 genes were detected, although there was a 47-fold increase in hepatic ACVRL1 expression compared with age-matched control liver. To the authors' knowledge, this is the first report of chylous ascites resulting from peliosis hepatis in any species.
• Analysis of lead distribution in avian organs by LA-ICP-MS: Study of experimentally lead-exposed ducks and kites
  Ryouta Torimoto; Chihiro Ishii; Hiroshi Sato; Keisuke Saito; Yukiko Watanabe; Kohei Ogasawara; Ayano Kubota; Takehisa Matsukawa; Kazuhito Yokoyama; Atsushi Kobayashi; Takashi Kimura; Shouta M.M. Nakayama; Yoshinori Ikenaka; Mayumi Ishizuka
  Environmental Pollution, 283, 117086, 117086, Elsevier BV, 2021年08月, ［査読有り］, ［国際誌］
  英語, 研究論文（学術雑誌）, Lead poisoning of wild birds by ingestion of lead ammunition occurs worldwide. Histopathological changes in organs of lead-intoxicated birds are widely known, and lead concentration of each organ is measurable using mass spectrometry. However, detailed lead localization at the suborgan level has remained elusive in lead-exposed birds. Here we investigated the detailed lead localization in organs of experimentally lead-exposed ducks and kites by laser ablation inductively coupled plasma mass spectrometry (LA-ICP-MS). In both the ducks and kites, lead accumulated diffusely in the liver, renal cortex, and brain. Lead accumulation was restricted to the red pulp in the spleen. With regard to species differences in lead distribution patterns, it is noteworthy that intensive lead accumulation was observed in the arterial walls only in the kites. In addition, the distribution of copper in the brain was altered in the lead-exposed ducks. Thus, the present study shows suborgan lead distribution in lead-exposed birds and its differences between avian species for the first time. These findings will provide fundamental information to understand the cellular processes of lead poisoning and the mechanisms of species differences in susceptibility to lead exposure.
• KDM2B promotes cell viability by enhancing DNA damage response in canine hemangiosarcoma
  Kevin Christian Montecillo Gulay; Keisuke Aoshima; Yuki Shibata; Hironobu Yasui; Qin Yan; Atsushi Kobayashi; Takashi Kimura
  Journal of Genetics and Genomics, 48, 7, 618, 630, Elsevier BV, 2021年07月, ［査読有り］, ［国際誌］
  英語, 研究論文（学術雑誌）, Epigenetic regulators have been implicated in tumorigenesis of many types of cancer; however, their roles in endothelial cell cancers such as canine hemangiosarcoma (HSA) have not been studied. In this study, we find that lysine-specific demethylase 2b (KDM2B) is highly expressed in HSA cell lines compared with normal canine endothelial cells. Silencing of KDM2B in HSA cells results in increased cell death in vitro compared with the scramble control by inducing apoptosis through the inactivation of the DNA repair pathways and accumulation of DNA damage. Similarly, doxycycline-induced KDM2B silencing in tumor xenografts results in decreased tumor sizes compared with the control. Furthermore, KDM2B is also highly expressed in clinical cases of HSA. We hypothesize that pharmacological KDM2B inhibition can also induce HSA cell death and can be used as an alternative treatment for HSA. We treat HSA cells with GSK-J4, a histone demethylase inhibitor, and find that GSK-J4 treatment also induces apoptosis and cell death. In addition, GSK-J4 treatment decreases tumor size. Therefore, we demonstrate that KDM2B acts as an oncogene in HSA by enhancing the DNA damage response. Moreover, we show that histone demethylase inhibitor GSK-J4 can be used as a therapeutic alternative to doxorubicin for HSA treatment.
• Minocycline prevents primary duck neurons from duck Tembusu virus-induced death
  Sittinee KULPRASERTSRI; Keisuke AOSHIMA; Atsushi KOBAYASHI; Takashi KIMURA
  Journal of Veterinary Medical Science, 83, 4, 734, 741, Japanese Society of Veterinary Science, 2021年, ［査読有り］, ［最終著者, 責任著者］
  研究論文（学術雑誌）
• Long interspersed nucleotide element‐1 hypomethylation in canine malignant mucosal melanoma
  Teita Ishizaki; Jumpei Yamazaki; Shinji Meagawa; Nozomu Yokoyama; Keisuke Aoshima; Mitsuyoshi Takiguchi; Takashi Kimura
  Veterinary and Comparative Oncology, 18, 4, 854, 860, Wiley, 2020年12月, ［査読有り］, ［国際誌］
  英語, 研究論文（学術雑誌）, Canine malignant melanoma is a common cancer with a high mortality rate and is a clinically important disease. DNA methylation has been considered to be a potential tumorigenic mechanism through aberrant DNA methylation at promoter region which represses gene transcription. Global hypomethylation could also facilitate chromosome instability. There are few reports regarding DNA methylation in canine malignant melanoma; therefore, the purpose of this study was to examine DNA methylation status of long interspersed nucleotide element-1 (LINE-1) to be a surrogate marker of genome-wide methylation changes in this disease. We measured levels of DNA methylation of two adjacent cytosine-guanine sites on CpG island (CGI) at the putative promoter of canine LINE-1 sequence by bisulphite-pyrosequencing in 41 canine melanoma patient samples as well as six cell lines compared with normal mucosae. The survival rates were obtained from owners or medical records. We found DNA methylation levels of LINE-1 in normal mucosae were methylated. Interestingly, both melanoma cell lines and clinical melanoma samples showed remarkable hypomethylation. In addition, patients with lower LINE-1 methylation showed worse prognosis than those with higher LINE-1 methylation, though the difference did not reach statistical significance (P = .09). Here, we demonstrate that hypomethylation of LINE-1 is an epigenetically aberrant feature in canine melanoma with possible prognostic value.
• Pathological and Immunohistochemical Analyses of Naturally Occurring Equine Glanders Using an Anti-BpaB Antibody
  Ochbayar Erdemsurakh; Baatarjargal Purevdorj; Khurtsbaatar Ochirbat; Altanchimeg Adilbish; Batbaatar Vanaabaatar; Keisuke Aoshima; Atsushi Kobayashi; Takashi Kimura
  Veterinary Pathology, 57, 6, 807, 811, SAGE Publications, 2020年11月, ［査読有り］, ［最終著者, 責任著者］
  研究論文（学術雑誌）, Glanders is caused by the gram-negative bacterium Burkholderia mallei. In this study, we investigated the histopathology and immunohistochemical localization of B. mallei in natural cases of equine glanders. Four horses showing clinical signs of nasal discharge and multiple cutaneous nodules or papulae in the hindlimbs and abdomen were reported in Mongolia. They tested positive for B. mallei infection on complement fixation, Rose Bengal agglutination, and mallein tests. Gross and histological lesions observed in these cases were similar to those previously reported in equine glanders. Immunohistochemistry using a monoclonal antibody to B. mallei BpaB showed localization of the bacterial antigen in the cytoplasm of neutrophils, macrophages, epithelioid cells, and multinucleated giant cells in the pyogranulomas and abscesses in target organs. Some alveolar type II cells and bronchiolar epithelial cells also contained the antigen. These results suggest that the anti-BpaB antibody is useful for identifying B. mallei–infected cell types in naturally infected horses.
• Wobbly hedgehog syndrome with disseminated histiocytic sarcoma and lateral ventricular meningioma in an African pygmy hedgehog
  Lesa A. Thompson; Atsuya Morita; Shoko Murakami; Noboru Sasaki; Miou Murashita; Ryou Yamazaki; Atsushi Kobayashi; Takashi Kimura; Mitsuyoshi Takiguchi
  J Vet Diagn Invest, 32, 6, 953, 956, SAGE Publications, 2020年11月, ［査読有り］, ［国際誌］
  英語, 研究論文（学術雑誌）, An 8-mo-old male African pygmy hedgehog was anorectic and ataxic; physical examination revealed tetraparesis and a gangrenous left hindlimb. Analgesic and supportive care were administered, but the animal died 3 d after presentation. Postmortem examination revealed a histiocytic sarcoma in a mesenteric lymph node with metastasis to several organs, multifocal vacuolation in the cerebral and cerebellar white matter, and a meningioma in the left lateral ventricle. We diagnosed wobbly hedgehog syndrome (WHS) with disseminated histiocytic sarcoma and lateral ventricular meningioma. Ventricular meningioma, a rare neoplasm in veterinary and human patients, has not been reported previously in hedgehogs, to our knowledge. The neurologic signs in our case were probably caused by the WHS-related vacuolar lesions and are consistent with those of reported WHS cases. Duration of illness was shorter than is typical of WHS cases, which might be related to the disseminated histiocytic sarcoma. Clinical relevance of the lateral ventricular meningioma was not evident because the ventricular mass was localized and not invasive.
• Genome-wide DNA methylation analysis identifies promoter hypermethylation in canine malignant melanoma
  T. Ishizaki; J. Yamazaki; J. Jelinek; K. Aoshima; T. Kimura
  Research in Veterinary Science, 132, 521, 526, Elsevier BV, 2020年10月, ［査読有り］, ［国際誌］
  英語, 研究論文（学術雑誌）, Canine malignant melanoma is a common cancer with a high mortality rate. Although previous studies have evaluated various aspects of this tumour, the exact mechanism of tumourigenesis remains unknown. Epigenetic mechanisms, such as DNA methylation, have recently gained attention as aetiological factors for neoplasia in humans. This study aimed to analyse genome-wide DNA methylation patterns in canine malignant melanoma based on next-generation sequencing data. A total of 76,213 CpG sites, including 29,482 sites in CpG islands (CGIs), were analysed using next-generation sequencing of methylation-specific signatures, obtained by sequential digestion with enzymes, to compare normal oral mucosal samples from four healthy dogs, four canine melanoma cell lines (3 oral cavity and 1 skin), and five clinical samples of oral canine melanoma. Malignant melanoma showed increased methylation at thousands of normally unmethylated CpG sites in CGIs and decreased methylation at normally methylated CpG sites in non-CGIs. Interestingly, the promoter regions of 81-393 genes were hypermethylated; 23 of these genes were present in all melanoma cell lines and melanoma clinical samples. Among these 23 genes, six genes with "sequence-specific DNA binding" annotation were significantly enriched, including three Homeobox genes-HMX2, TLX2, and HOXA9-that may be involved in the tumourigenesis of canine malignant melanoma. This study revealed widespread alterations in DNA methylation and a large number of hypermethylated genes in canine malignant melanoma.
• Susceptibility of rat immortalized neuronal cell line Rn33B to equine herpesvirus-1 infection is differentiation-dependent
  Minato E; Kobayashi A; Aoshima K; Fukushi H; Kimura T
  Microbiol Immunol, 64, 2, 123, 132, Wiley, 2020年02月, ［査読有り］, ［最終著者, 責任著者］, ［国際誌］
  英語, 研究論文（学術雑誌）, Equine herpesvirus-1 (EHV-1), which causes encephalomyelitis in horses, shows endotheliotropism in the central nervous system of horses, and generally does not infect neurons. However, little is known about the mechanism underlying the resistance of neuron to EHV-1, due to the lack of convenient cell culture systems. In this study, we examined EHV-1 infection in immortalized Rn33B rat neuronal cells, which differentiate into neurons when cultured under nonpermissive conditions. Because murine cell lines are resistant to EHV-1 infections due to the lack of functional entry receptors for EHV-1, we used an Rn33B-derived cell line that stably expresses the equine MHC class 1 molecule, which acts as EHV-1 entry receptor (Rn33B-A68B2M cells). EHV-1 infected undifferentiated Rn33B-A68B2M cells more efficiently than differentiated cells, resulting in the production of progeny virus in the former but not in the latter. By contrast, both differentiated and undifferentiated cells infected with herpes simplex virus-1 produced infectious viral progeny. While EHV-1 infection induced stronger expression of IFN alpha gene in differentiated cells than in undifferentiated cells, downstream IFN responses, including phosphorylation of STAT1 (signal transducer and activator of transcription 1) and expression of IFN-stimulated genes, were not activated regardless of whether cells were differentiated or not. These results suggest that neuronal differentiation of RN33B-A68B2M cells reduced their susceptibility to EHV-1, which is not due to different IFN responses. This culture system may be useful as an in vitro model for studying neuron-specific resistance to EHV-1, by investigating viral and host factors responsible for the difference in susceptibility between differentiated and undifferentiated cells.
• Seroprevalence of equine glanders in horses in the central and eastern parts of Mongolia
  Ochbayar ERDEMSURAKH; Khurtsbaatar OCHIRBAT; Ulziisaikhan GOMBOSUREN; Batbold TSERENDORJ; Baatarjargal PUREVDORJ; Batbaatar VANAABAATAR; Keisuke AOSHIMA; Atsushi KOBAYASHI; Takashi KIMURA
  Journal of Veterinary Medical Science, 82, 9, 1247, 1252, Japanese Society of Veterinary Science, 2020年, ［査読有り］, ［最終著者, 責任著者］, ［国内誌］
  英語, 研究論文（学術雑誌）, Glanders is a contagious and fatal equine disease caused by the gram-negative bacterium Burkholderia mallei.B. mallei is prevalent among horse populations in Asia, the Middle East, and South America. More than four million horses have been registered in Mongolia in 2020. However, the resent prevalence of glanders has not been well investigated. In this study, we aimed to investigate the seropositivity of B. mallei in horse populations in Mongolia using the complement fixation test (CFT) and Rose Bengal plate agglutination test (RBT). We randomly collected blood samples from horses in central and eastern Mongolia between 2018 and 2019. Of 337 horses, 26 (7.7%) and 28 (8.3%) were seropositive using RBT and CFT, respectively. Interestingly, seropositivity in horses resulting from crossbreeding of Mongolian native horses with thoroughbred horses was higher than that in Mongolian native horses. Our observations suggest that equine glanders are still endemic to Mongolia.
• High drug efflux pump capacity and low DNA damage response induce doxorubicin resistance in canine hemangiosarcoma cell lines.
  Atsuya Morita; Keisuke Aoshima; Kevin Christian Montecillo Gulay; Shinichi Onishi; Yuki Shibata; Hironobu Yasui; Atsushi Kobayashi; Takashi Kimura
  Research in veterinary science, 127, 1, 10, Elsevier BV, 2019年12月, ［査読有り］
  研究論文（学術雑誌）, * Corresponding author
• Exogenous Expression of Equine MHC Class I Molecules in Mice Increases Susceptibility to Equine Herpesvirus 1 Pulmonary Infection.
  Minato E; Aoshima K; Kobayashi A; Ohnishi N; Sasaki N; Kimura T
  Veterinary pathology, 56, 5, 703, 710, SAGE Publications, 2019年09月, ［査読有り］, ［最終著者, 責任著者］
  研究論文（学術雑誌）, Equine herpesvirus 1 (EHV-1) uses equine major histocompatibility complex class I (MHC class I) as an entry receptor. Exogenous expression of equine MHC class I genes in murine cell lines confers susceptibility to EHV-1 infection. To examine the in vivo role of equine MHC class I as an entry receptor for EHV-1, we generated transgenic (Tg) mice expressing equine MHC class I under the control of the CAG promoter. Equine MHC class I protein was expressed in the liver, spleen, lung, and brain of Tg mice, which was confirmed by Western blot. However, equine MHC class I antigen was only detected in bronchiolar epithelium and not in other tissues, using the immunofluorescence method employed in this study. Both Tg and wild-type (WT) mice developed pneumonia 3 days after intranasal infection with EHV-1. The bronchiolar epithelial cells of Tg mice showed more severe necrosis, compared with those in WT mice. In addition, the number of virus antigen-positive cells in the lungs was higher in Tg mice than in WT mice. These results suggest that exogenous expression of equine MHC class I renders mice more susceptible to EHV-1 infection.
• A novel combination of prion strain co-occurrence in patients with sporadic Creutzfeldt-Jakob disease.
  Kobayashi A; Iwasaki Y; Takao M; Saito Y; Iwaki T; Qi Z; Torimoto R; Shimazaki T; Munesue Y; Isoda N; Sawa H; Aoshima K; Kimura T; Kondo H; Mohri S; Kitamoto T
  The American journal of pathology, 189, 6, 1276, 1283, Elsevier BV, 2019年06月, ［査読有り］, ［国際誌］
  英語, 研究論文（学術雑誌）, Six subgroups of sporadic Creutzfeldt-Jakob disease have been identified by distinctive clinicopathologic features, genotype at polymorphic codon 129 [methionine (M)/valine (V)] of the PRNP gene, and type of abnormal prion proteins (type 1 or 2). In addition to the pure subgroups, mixed neuropathologic features and the coexistence of two types of abnormal prion proteins in the same patient also have been reported. Here, we found that a portion of the patients previously diagnosed as MM1 had neuropathologic characteristics of the MM2 thalamic form (ie, neuronal loss of the inferior olivary nucleus of the medulla). Furthermore, coexistence of biochemical features of the MM2 thalamic form also was confirmed in the identified cases. In addition, in transmission experiments using prion protein-humanized mice, the brain material from the identified case showed weak infectivity and generated characteristic abnormal prion proteins in the inoculated mice resembling those after inoculation with brain material of MM2 thalamic form. Taken together, these results show that the co-occurrence of MM1 and MM2 thalamic form is a novel entity of sporadic Creutzfeldt-Jakob disease prion strain co-occurrence. The present study raises the possibility that the co-occurrence of the MM2 thalamic form might have been overlooked so far because of the scarcity of abnormal prion protein accumulation and restricted neuropathology.
• Ganglioside synthase knock-out reduces prion disease incubation time in mouse models.
  Kobayashi A; Qi Z; Shimazaki T; Munesue Y; Miyamoto T; Isoda N; Sawa H; Aoshima K; Kimura T; Mohri S; Kitamoto T; Yamashita T; Miyoshi I
  The American journal of pathology, 189, 3, 677, 686, Elsevier BV, 2019年03月, ［査読有り］, ［国際誌］
  英語, 研究論文（学術雑誌）, Localization of the abnormal and normal isoforms of prion proteins to detergent-resistant membrane microdomains, lipid rafts, is important for the conformational conversion. Lipid rafts are enriched in sialic acid-containing glycosphingolipids (namely, gangliosides). Alteration in the ganglioside composition of lipid rafts can affect the localization of lipid raft-associated proteins. To investigate the role of gangliosides in the pathogenesis of prion diseases, we performed intracerebral transmission study of a scrapie prion strain Chandler and a Gerstmann-Sträussler-Scheinker syndrome prion strain Fukuoka-1 using various knockout mouse strains ablated with ganglioside synthase gene (ie, GD2/GM2 synthase, GD3 synthase, or GM3 synthase). After challenge with the Chandler strain, GD2/GM2 synthase knockout mice showed 20% reduction of incubation time, reduced prion protein deposition in the brain with attenuated glial reactions, and reduced localization of prion proteins to lipid rafts. These results raise the possibility that the gangliosides may have an important role in prion disease pathogenesis by affecting the localization of prion proteins to lipid rafts.
• Stat3 is indispensable for damage‐induced crypt regeneration but not for Wnt‐driven intestinal tumorigenesis
  Hiroko Oshima; Sau-Yee Kok; Mizuho Nakayama; Kazuhiro Murakami; Dominic Chih-Cheng Voon; Takashi Kimura; Masanobu Oshima
  The FASEB Journal, 33, 2, 1873, 1886, Wiley, 2019年02月, ［査読有り］, ［国際誌］
  英語, 研究論文（学術雑誌）, Signal transducer and activator of transcription 3 (Stat3) has been shown to play a role in intestinal regeneration and colitis-associated colon carcinogenesis. However, the role of Stat3 in the Wnt-driven sporadic intestinal tumorigenesis remains poorly understood. We examined the roles of Stat3 in intestinal regeneration and tumorigenesis by organoid culture experiments using Stat3∆IEC mouse-derived intestinal epithelial cells in which Stat3 was disrupted. The regeneration of intestinal mucosa and organoid formation were significantly suppressed by Stat3 disruption, which was compensated by Wnt activation. Furthermore, once organoids were recovered, Stat3 was no longer required for organoid growth. These results indicate that Stat3 and Wnt signaling cooperatively protect epithelial cells at the early phase of intestinal regeneration. In contrast, intestinal tumorigenesis was not suppressed by Stat3 disruption in adenomatous polyposis coli ( Apc) Δ716 and Apc∆716 Tgfbr2∆IEC mice, thus indicating that Stat3 is not required for Wnt activation-driven intestinal tumorigenesis. Mechanistically, Itga5 and Itga6 were down-regulated by Stat3 disruption, and focal adhesion kinase (FAK) activation was also suppressed. Notably, FAK inhibitor suppressed the organoid formation of wild-type epithelial cells. These results indicate that Stat3 is indispensable for the survival of epithelial cells through the activation of integrin signaling and the downstream FAK pathway; however, it is not required for the Wnt signaling-activated normal or tumor epithelial cells.-Oshima, H., Kok, S.-Y., Nakayama, M., Murakami, K., Voon, D. C.-C., Kimura, T., Oshima, M. Stat3 is indispensable for damage-induced crypt regeneration but not for Wnt-driven intestinal tumorigenesis.
• Notch2 signal is required for the maintenance of canine hemangiosarcoma cancer stem cell-like cells
  Keisuke Aoshima; Yuki Fukui; Kevin Christian Montecillo Gulay; Ochbayar Erdemsurakh; Atsuya Morita; Atsushi Kobayashi; Takashi Kimura
  BMC Veterinary Research, 14, 1, 301, Springer Nature America, Inc, 2018年12月, ［査読有り］
  研究論文（学術雑誌）, * Corresponding author
• Generation and validation of novel anti-bovine CD163 monoclonal antibodies ABM-1A9 and ABM-2D6
  Shimamoto Y; Nio-Kobayashi J; Watarai H; Nagano M; Saito N; Takahashi E; Higuchi H; Kobayashi A; Kimura T; Kitamura H
  Vet Immunol Immunopathol, 198, 6, 13, Elsevier BV, 2018年04月, ［査読有り］
  英語, 研究論文（学術雑誌）
• Detection of novel gammaherpesviruses from fruit bats in Indonesia.
  Wada Y; Sasaki M; Setiyono A; Handharyani E; Rahmadani I; Taha S; Adiani S; Latief M; Kholilullah ZA; Subangkit M; Kobayashi S; Nakamura I; Kimura T; Orba Y; Sawa H
  Journal of medical microbiology, 67, 3, 415, 422, Microbiology Society, 2018年03月01日, ［査読有り］, ［国際誌］
  英語, 研究論文（学術雑誌）, Bats are an important natural reservoir of zoonotic viral pathogens. We previously isolated an alphaherpesvirus in fruit bats in Indonesia, and here establish the presence of viruses belonging to other taxa of the family Herpesviridae. We screened the same fruit bat population with pan-herpesvirus PCR and discovered 68 sequences of novel gammaherpesvirus, designated 'megabat gammaherpesvirus' (MgGHV). A phylogenetic analysis of approximately 3.4 kbp of continuous MgGHV sequences encompassing the glycoprotein B gene and DNA polymerase gene revealed that the MgGHV sequences are distinct from those of other reported gammaherpesviruses. Further analysis suggested the existence of co-infections of herpesviruses in Indonesian fruit bats. Our findings extend our understanding of the infectious cycles of herpesviruses in bats in Indonesia and the phylogenetic diversity of the gammaherpesviruses.
• Development of a quick bioassay for the evaluation of transmission properties of acquired prion diseases.
  Munesue Y; Shimazaki T; Qi Z; Isoda N; Sawa H; Aoshima K; Kimura T; Mohri S; Kitamoto T; Kobayashi A
  Neuroscience letters, 668, 43, 47, Elsevier BV, 2018年03月, ［査読有り］, ［国際誌］
  英語, 研究論文（学術雑誌）, Evaluation of transmission properties is important for the differential diagnosis of a subgroup of acquired Creutzfeldt-Jakob disease (CJD) with methionine homozygosity at polymorphic codon 129 of the PRNP gene, an intermediate type abnormal prion protein (PrP), and kuru plaques, denoted as acquired CJD-MMiK. The present study aimed to develop a quick evaluation system of the transmission properties of acquired CJD-MMiK. In the PrP-humanized mice intraperitoneally inoculated with brain homogenates from an acquired CJD-MMiK patient, accumulation of abnormal PrP was observed in follicular dendritic cells of the spleen at 75 days post-inoculation. The transmission properties of acquired CJD-MMiK were quite different from those of sporadic CJD with the same PRNP codon 129 genotype. Moreover, even at 14 days post-inoculation, the characteristic transmission properties of acquired CJD-MMiK could be detected. These findings suggest that the bioassay using follicular dendritic cells of the spleen, named as a FDC assay, can be an easy, time-saving, and useful method to distinguish acquired CJD-MMiK from sporadic CJD.
• A large osteosarcoma in the mandible of an ox
  K.E. Mwape; V.C. Zulu; I.K. Phiri; J. Yabe; N. Nishida; K. Aoshima; Y. Qiu; T. Kimura; G.S. Pandey
  Indian Journal of Veterinary Pathology, 42, 2, 119, 119, Diva Enterprises Private Limited, 2018年, ［査読有り］
  英語, 研究論文（学術雑誌）
• Dembo-PCR technique for the detection of bovine abortion, diarrhea, and respiratory disease complex infectious agents in potential vectors and reservoirs
  Rahpaya SS; Tsuchiaka S; Kishimoto M; Oba M; Katayama Y; Nunomura Y; Kokawa S; Kimura T; Kobayashi A; Kirino Y; Okabayashi T; Nonaka N; Mekata H; Aoki H; Shiokawa M; Umetsu M; Morita T; Hasebe A; Otsu K; Asai T; Yamaguchi T; Makino S; Murata Y; Abi AJ; Omatsu T; Mizutani T
  J Vet Sci, 19, 3, 350, 350, The Korean Society of Veterinary Science, 2018年, ［査読有り］, ［国際誌］
  英語, 研究論文（学術雑誌）, Bovine abortion, diarrhea, and respiratory disease complexes, caused by infectious agents, result in high and significant economic losses for the cattle industry. These pathogens are likely transmitted by various vectors and reservoirs including insects, birds, and rodents. However, experimental data supporting this possibility are scarce. We collected 117 samples and screened them for 44 bovine abortive, diarrheal, and respiratory disease complex pathogens by using Dembo polymerase chain reaction (PCR), which is based on TaqMan real-time PCR. Fifty-seven samples were positive for at least one pathogen, including bovine viral diarrhea virus, bovine enterovirus, Salmonella enterica ser. Dublin, Salmonella enterica ser. Typhimurium, and Neospora caninum; some samples were positive for multiple pathogens. Bovine viral diarrhea virus and bovine enterovirus were the most frequently detected pathogens, especially in flies, suggesting an important role of flies in the transmission of these viruses. Additionally, we detected the N. caninum genome from a cockroach sample for the first time. Our data suggest that insects (particularly flies), birds, and rodents are potential vectors and reservoirs of abortion, diarrhea, and respiratory infectious agents, and that they may transmit more than one pathogen at the same time.
• Cellular atypia is negatively correlated with immunohistochemical reactivity of CD31 and vWF expression levels in canine hemangiosarcoma.
  Aprilia MAHARANI; Keisuke AOSHIMA; Shinichi ONISHI; Kevin Christian Montecillo GULAY; Atsushi KOBAYASHI; Takashi KIMURA
  The Journal of veterinary medical science, 80, 2, 213, 218, Japanese Society of Veterinary Science, 2018年, ［査読有り］
  研究論文（学術雑誌）, * Corresponding author
• The full genome sequences of 8 equine herpesvirus type 4 isolates from horses in Japan
  Satoko IZUME; Rikio KIRISAWA; Kenji OHYA; Aiko OHNUMA; Takashi KIMURA; Tsutomu OMATSU; Yukie KATAYAMA; Tetsuya MIZUTANI; Hideto FUKUSHI
  Journal of Veterinary Medical Science, 79, 1, 206, 212, 2017年, ［査読有り］
  英語, 研究論文（学術雑誌）
• Use of Histone K-M Mutants for the Analysis of Transcriptional Regulation in Mouse Zygotes.
  Aoshima K; Kimura T; Okada Y
  Methods in molecular biology (Clifton, N.J.), 1605, 259, 270, Springer New York, 2017年, ［査読有り］
  論文集(書籍)内論文
• Rapid and broad detection of H5 hemagglutinin by an immunochromatographic kit using novel monoclonal antibody against highly pathogenic avian influenza virus belonging to the genetic clade 2.3.4.4.
  Nguyen LT; Nakaishi K; Motojima K; Ohkawara A; Minato E; Maruyama J; Hiono T; Matsuno K; Okamatsu M; Kimura T; Takada A; Kida H; Sakoda Y
  PloS one, 12, 8, e0182228, 2017年, ［査読有り］
  研究論文（学術雑誌）
• Divergent bufavirus harboured in megabats represents a new lineage of parvoviruses.
  Sasaki M; Gonzalez G; Wada Y; Setiyono A; Handharyani E; Rahmadani I; Taha S; Adiani S; Latief M; Kholilullah ZA; Subangkit M; Kobayashi S; Nakamura I; Kimura T; Orba Y; Ito K; Sawa H
  Scientific reports, 6, 1, 24257, 24257, Nature Publishing Group, 2016年04月, ［査読有り］
  英語, 研究論文（学術雑誌）, Bufavirus is a recently recognized member of the genus Protoparvovirus in the subfamily Parvovirinae. It has been reported that human bufavirus was detected predominantly in patients with diarrhoea in several countries. However, little is known about bufavirus or its close relatives in nonhuman mammals. In this study, we performed nested-PCR screening and identified bufavirus from 12 megabats of Pteropus spp. in Indonesia. Furthermore, we determined nearly the full genome sequence of a novel megabat-borne bufavirus, tentatively named megabat bufavirus 1. Phylogenetic analyses showed that megabat bufavirus 1 clustered with known protoparvoviruses, including human bufavirus but represented a distinct lineage of bufavirus. Our analyses also inferred phylogenetic relationships among animal-borne bufaviruses recently reported by other studies. Recombination analyses suggested that the most common recent ancestor of megabat bufavirus 1 might have arisen from multiple genetic recombination events. These results characterized megabat bufavirus 1 as the first protoparvovirus discovered from megabats and indicates the high genetic divergence of bufavirus.
• Detection of novel polyomaviruses in fruit bats in Indonesia.
  Kobayashi S; Sasaki M; Nakao R; Setiyono A; Handharyani E; Orba Y; Rahmadani I; Taha S; Adiani S; Subangkit M; Nakamura I; Kimura T; Sawa H
  Archives of virology, 160, 4, 1075, 1082, 4, 2015年04月, ［査読有り］, ［責任著者］
  研究論文（学術雑誌）
• Detection of coronavirus genomes in Moluccan naked-backed fruit bats in Indonesia.
  Anindita PD; Sasaki M; Setiyono A; Handharyani E; Orba Y; Kobayashi S; Rahmadani I; Taha S; Adiani S; Subangkit M; Nakamura I; Sawa H; Kimura T
  Archives of virology, 160, 4, 1113, 1118, 4, 2015年04月, ［査読有り］, ［責任著者］
  英語, 研究論文（学術雑誌）, Bats have been shown to serve as natural reservoirs for numerous emerging viruses including severe acute respiratory syndrome coronavirus (SARS-CoV). In the present study, we report the discovery of bat CoV genes in Indonesian Moluccan naked-backed fruit bats (Dobsonia moluccensis). A partial RNA-dependent RNA polymerase gene sequence was detected in feces and tissues samples from the fruit bats, and the region between the RdRp and helicase genes could also be amplified from fecal samples. Phylogenetic analysis suggested that these bat CoVs are related to members of the genus Betacoronavirus.
• Autophagy inhibits viral genome replication and gene expression stages in West Nile virus infection.
  Kobayashi S; Orba Y; Yamaguchi H; Takahashi K; Sasaki M; Hasebe R; Kimura T; Sawa H
  Virus research, 191, 83, 91, Elsevier, 2014年10月, ［査読有り］
  英語, Autophagy is a lysosomal degradation pathway that is implicated in many viral infections. However, its role in West Nile virus (WNV) infection remains controversial. In the present study, we examined the relationship between WNV infection and autophagy in infected cells. We demonstrated that LC3-II expression, a molecular marker for autophagosomal membranes, was enhanced in WNV-infected cells 6 h post-infection. LC3-II expression was further enhanced in WNV-inoculated cells when treated with a lysosomal protease inhibitor. Meanwhile, WNV replication in cells lacking Atg5, an essential factor for autophagy, was increased compared with replication in wild-type cells. In addition, WNV replication was inhibited in cells lacking Atg5 when they were transfected with an ATG5 expression plasmid. These results suggest an antiviral role for autophagy in WNV-infected cells. We also examined which viral replication stages were affected by autophagy by using a Tat-beclin 1 peptide to induce autophagy and pseudo-infectious WNV reporter virus particles (WNV-RVPs) that monitor viral genome replication and gene expression stages via GFP expression. We found that autophagy induction in HeLa cells by Tat-beclin 1 peptide 3 h after WNV inoculation inhibited viral replication, and GFP expression was significantly inhibited in wild-type cells when compared with cells lacking Atg5. Taken together, these results suggest that autophagy is induced by WNV infection, and that this induction inhibits WNV replication at the viral genome replication and gene expression stages. (C) 2014 Elsevier B.V. All rights reserved.
• Isolation and characterization of a novel alphaherpesvirus in fruit bats.
  Sasaki Michihito; Setiyono Agus; Handharyani Ekowati; Kobayashi Shintaro; Rahmadani Ibenu; Taha Siswatiana; Adiani Sri; Subangkit Mawar; Nakamura Ichiro; Sawa Hirofumi; Kimura Takashi
  Journal of virology, 88, 17, 9819, 9829, American Society for Microbiology, 2014年09月01日, ［査読有り］, ［最終著者, 責任著者］
  英語, 研究論文（学術雑誌）, Bats are known to harbor emerging RNA viruses. Recent studies have used high-throughput sequencing technology to identify various virus species, including DNA viruses that are harbored by bats; however, little is known about the nature of these potentially novel viruses. Here, we report the characterization of a novel herpesvirus isolated from an Indonesian pteropodid bat. The virus, tentatively named fruit bat alphaherpesvirus 1 (FBAHV1), has a double-stranded DNA genome of 149,459 bp. The phylogenetic analyses suggested that FBAHV1 is phylogenetically grouped with simplexviruses within the subfamily Alphaherpesvirinae. Inoculation of FBAHV1 into laboratory mice caused a lethal infection. Virus infection was observed in lung, liver, and brain tissue. Serological and PCR screening revealed that fruit bats infected with FBAHV1 or its related virus are widely distributed in Indonesia. The identification of FBAHV1 makes a considerable contribution to our understanding of simplexviruses associated with bats.
• Role of the C-terminal region of vervet monkey polyomavirus 1 VP1 in virion formation.
  Yamaguchi H; Kobayashi S; Maruyama J; Sasaki M; Takada A; Kimura T; Sawa H; Orba Y
  The Journal of veterinary medical science / the Japanese Society of Veterinary Science, 76, 5, 637, 644, 5, 2014年05月, ［査読有り］
  英語, Recently, we detected novel vervet monkey polyomavirus 1 (VmPyV) in a vervet monkey. Among amino acid sequences of major capsid protein VP1s of other polyomaviruses, VmPyV VP1 is the longest with additional amino acid residues in the C-terminal region. To examine the role of VmPyV VP1 in virion formation, we generated virus-like particles (VLPs) of VmPyV VP1, because VLP is a useful tool for the investigation of the morphological characters of polyomavirus virions. After the full-length VmPyV VP1 was subcloned into a mammalian expression plasmid, the plasmid was transfected into human embryonic kidney 293T (HEK293T) cells. Thereafter, VmPyV VLPs were purified from the cell lysates of the transfected cells via sucrose gradient sedimentation. Electron microscopic analyses revealed that VmPyV VP1 forms VLPs with a diameter of approximately 50 nm that are exclusively localized in cell nuclei. Furthermore, we generated VLPs consisting of the deletion mutant VmPyV VP1 (ΔC VP1) lacking the C-terminal 116 amino acid residues and compared its VLP formation efficiency and morphology to those of VLPs from wild-type VmPyV VP1 (WT VP1). WT and ΔC VP1 VLPs were similar in size, but the number of ΔC VP1 VLPs was much lower than that of WT VP1 VLPs in VP1-expressing HEK293T cells. These results suggest that the length of VP1 is unrelated to virion morphology; however, the C-terminal region of VmPyV VP1 affects the efficiency of its VLP formation.
• Molecular epidemiology of paramyxoviruses in frugivorous Eidolon helvum bats in Zambia.
  Muleya W; Sasaki M; Orba Y; Ishii A; Thomas Y; Nakagawa E; Ogawa H; Hang'ombe B; Namangala B; Mweene A; Takada A; Kimura T; Sawa H
  The Journal of veterinary medical science, 76, 4, 611, 614, JAPANESE SOCIETY OF VETERINARY SCIENCE, 2014年04月, ［査読有り］
  英語, In this study, we describe the detection of novel paramyxoviruses from the Eidolon helvum species of fruit bats. We extracted RNA from 312 spleen samples from bats captured in Zambia over a period of 4 years (2008–2011). Semi-nested RT-PCR detected a total of 25 (8%) positive samples for paramyxoviruses which were then directly sequenced and analyzed using phylogenetic analysis. Among the positive samples, seven novel paramyxoviruses were detected. Five viruses were closely related to the genus Henipavirus, while two viruses were related to the unclassified Bat paramyxoviruses from Ghana and Congo Brazzaville. Our study identified novel Henipavirus-related and unrelated viruses using RT-PCR in fruit bats from Kansaka National Park and indicated the presence of similar Bat paramyxoviruses originating from wide geographic areas, suggesting the ability of bats to harbor and transmit viruses. The presence of these viruses in fruit bats might pose a public health risk.
• Molecular epidemiology of paramyxoviruses in Zambian wild rodents and shrews.
  Sasaki M; Muleya W; Ishii A; Orba Y; Hang'ombe BM; Mweene AS; Moonga L; Thomas Y; Kimura T; Sawa H
  The Journal of general virology, 95, 2, 325, 330, Pt 2, 2014年02月, ［査読有り］
  英語, Rodents and shrews are known to harbour various viruses. Paramyxoviruses have been isolated from Asian and Australian rodents, but little is known about them in African rodents. Recently, previously unknown paramyxovirus sequences were found in South African rodents. To date, there have been no reports related to the presence and prevalence of paramyxoviruses in shrews. We found a high prevalence of paramyxoviruses in wild rodents and shrews from Zambia. Seminested reverse transcription-PCR assays were used to detect paramyxovirus RNA in 21% (96/ 462) of specimens analysed. Phylogenetic analysis revealed that these viruses were novel paramyxoviruses and could be classified as morbillivirus- and henipavirus-related viruses, and previously identified rodent paramyxovirus-related viruses. Our findings suggest the circulation of previously unknown paramyxoviruses in African rodents and shrews, and provide new information regarding the geographical distribution and genetic diversity of paramyxoviruses.
• Full genome sequences of zebra-borne equine herpesvirus type 1 isolated from zebra, Onager and Thomson’s gazelle
  Xiaoqin Guo; Satoko Izume; Ayaka Okada; Kenji Ohya; Kenji Ohya; Takashi Kimura; Hideto Fukushi; Hideto Fukushi
  Journal of Veterinary Medical Science, 76, 9, 1309, 1312, JAPANESE SOCIETY OF VETERINARY SCIENCE, 2014年01月, ［査読有り］
  英語, A strain of equine herpesvirus type 1 (EHV-1) was isolated from zebra. This strain, called “zebra-borne EHV-1”, was also isolated from an onager and a gazelle in zoological gardens in U.S.A. The full genome sequences of the 3 strains were determined. They shared 99% identities with each other, while they shared 98% and 95% identities with the horse derived EHV-1 and equine herpesvirus type 9, respectively. Sequence data indicated that the EHV-1 isolated from a polar bear in Germany is one of the zebra-borne EHV-1 and not a recombinant virus. These results indicated that zebra-borne EHV-1 is a subtype of EHV-1.
• Establishment of tracking system for West Nile virus entry and evidence of microtubule involvement in particle transport.
  Makino Y; Suzuki T; Hasebe R; Kimura T; Maeda A; Takahashi H; Sawa H
  Journal of virological methods, 195, 250, 257, Elsevier BV, 2014年01月, ［査読有り］
  研究論文（学術雑誌）
• Characterization of Japanese encephalitis virus infection in an immortalized mesencephalic cell line, CSM14.1.
  Kimura T; Okumura M; Kim E; Sasaki M; Orba Y; Sawa H
  Microbiology and immunology, 57, 10, 723, 731, 10, 2013年10月, ［査読有り］, ［筆頭著者, 責任著者］
  英語
• インドネシア共和国に生息するオオコウモリから分離した新規ヘルペスウイルスの性状解析
  佐々木 道仁; Agus Setiyono; Ekowati Handharyani; 中村 一郎; 澤 洋文; 木村 享史
  日本獣医学会学術集会講演要旨集, 156回, 283, 283, (公社)日本獣医学会, 2013年08月
  日本語
• オートファジーによるウエストナイルウイルス増殖抑制機構の解明
  小林 進太郎; 大場 靖子; 山口 宏樹; 佐々木 道仁; 長谷部 理絵; 木村 享史; 澤 洋文
  日本獣医学会学術集会講演要旨集, 156回, 267, 267, (公社)日本獣医学会, 2013年08月
  日本語
• Identification of a novel polyomavirus from vervet monkeys in Zambia
  Hiroki Yamaguchi; Shintaro Kobayashi; Akihiro Ishii; Hirohito Ogawa; Ichiro Nakamura; Ladslav Moonga; Bernard M. Hang'ombe; Aaron S. Mweene; Yuka Thomas; Takashi Kimura; Hirofumi Sawa; Yasuko Orba
  Journal of General Virology, 94, 6, 1357, 1364, 2013年06月01日, ［査読有り］
  英語, 研究論文（学術雑誌）
• Heterosubtypic antiviral activity of hemagglutinin-specific antibodies induced by intranasal immunization with inactivated influenza viruses in mice.
  Muramatsu M; Yoshida R; Miyamoto H; Tomabechi D; Kajihara M; Maruyama J; Kimura T; Manzoor R; Ito K; Takada A
  PloS one, 8, 8, e71534, Public Library of Science, 2013年, ［査読有り］
  英語, Influenza A virus subtypes are classified on the basis of the antigenicity of their envelope glycoproteins, hemagglutinin (HA; H1-H17) and neuraminidase. Since HA-specific neutralizing antibodies are predominantly specific for a single HA subtype, the contribution of antibodies to the heterosubtypic immunity is not fully understood. In this study, mice were immunized intranasally or subcutaneously with viruses having the H1, H3, H5, H7, H9, or H13 HA subtype, and cross-reactivities of induced IgG and IgA antibodies to recombinant HAs of the H1-H16 subtypes were analyzed. We found that both subcutaneous and intranasal immunizations induced antibody responses to multiple HAs of different subtypes, whereas IgA was not detected remarkably in mice immunized subcutaneously. Using serum, nasal wash, and trachea-lung wash samples of H9 virus-immunized mice, neutralizing activities of cross-reactive antibodies were then evaluated by plaque-reduction assays. As expected, no heterosubtypic neutralizing activity was detected by a standard neutralization test in which viruses were mixed with antibodies prior to inoculation into cultured cells. Interestingly, however, a remarkable reduction of plaque formation and extracellular release of the H12 virus, which was bound by the H9-induced cross-reactive antibodies, was observed when infected cells were subsequently cultured with the samples containing HA-specific cross-reactive IgA. This heterosubtypic plaque reduction was interfered when the samples were pretreated with anti-mouse IgA polyclonal serum. These results suggest that the majority of HA-specific cross-reactive IgG and IgA antibodies produced by immunization do not block cellular entry of viruses, but cross-reactive IgA may have the potential to inhibit viral egress from infected cells and thus to play a role in heterosubtypic immunity against influenza A viruses.
• Cysteine residues in the major capsid protein, Vp1, of the JC virus are important for protein stability and oligomer formation.
  Kobayashi S; Suzuki T; Igarashi M; Orba Y; Ohtake N; Nagakawa K; Niikura K; Kimura T; Kasamatsu H; Sawa H
  PloS one, 8, 10, e76668, 10, 2013年, ［査読有り］
  英語, The capsid of the human polyomavirus JC virus (JCV) consists of 72 pentameric capsomeres of a major structural protein, Vp1. The cysteine residues of the related Vp1 of SV40 are known to contribute to Vp1 folding, pentamer formation, pentamer-pentamer contacts, and capsid stabilization. In light of the presence of a slight structural difference between JCV Vp1 and SV40 counterpart, the way the former folds could be either different from or similar to the latter. We found a difference: an important contribution of Vp1 cysteines to the formation of infectious virions, unique in JCV and absent in SV40. Having introduced amino acid substitution at each of six cysteines (C42, C80, C97, C200, C247, and C260) in JCV Vp1, we found that, when expressed in HeLa cells, the Vp1 level was decreased in C80A and C247A mutants, and remained normal in the other mutants. Additionally, the C80A and C247A Vp1-expressing cell extracts did not show the hemagglutination activity characteristic of JCV particles. The C80A and C247A mutant Vp1s were found to be less stable than the wild-type Vp1 in HeLa cells. When produced in a reconstituted in vitro protein translation system, these two mutant proteins were stable, suggesting that some cellular factors were responsible for their degradation. As determined by their sucrose gradient sedimentation profiles, in vitro translated C247A Vp1 formed pentamers, but in vitro translated C80A Vp1 was entirely monomeric. When individually incorporated into the JCV genome, the C80A and C247A mutants, but not the other Vp1 cysteine residues mutants, interfered with JCV infectivity. Furthermore, the C80A, but not the C247A, mutation prevented the nuclear localization of Vp1 in JCV genome transfected cells. These findings suggest that C80 of JCV Vp1 is required for Vp1 stability and pentamer formation, and C247 is involved in capsid assembly in the nucleus.
• Human parainfluenza virus type 3 in wild nonhuman primates, Zambia.
  Sasaki M; Ishii A; Orba Y; Thomas Y; Hang'ombe BM; Moonga L; Mweene AS; Ogawa H; Nakamura I; Kimura T; Sawa H
  Emerging infectious diseases, 19, 9, 1500, 1503, Centers for Disease Control and Prevention, 2013年, ［査読有り］
  英語, Human parainfluenza virus type 3 (HPIV3) genome was detected in 4 baboons in Zambia. Antibody for HPIV3 was detected in 13 baboons and 6 vervet monkeys in 2 distinct areas in Zambia. Our findings suggest that wild nonhuman primates are susceptible to HPIV3 infection.
• Population genetic analysis and sub-structuring of Theileria parva in the northern and eastern parts of Zambia
  Walter Muleya; Boniface Namangala; Martin Simuunza; Ryo Nakao; Noboru Inoue; Takashi Kimura; Kimihito Ito; Chihiro Sugimoto; Hirofumi Sawa
  PARASITES & VECTORS, 5, 255, 2012年11月, ［査読有り］
  英語, 研究論文（学術雑誌）
• Molecular detection of a novel paramyxovirus in fruit bats from Indonesia
  Michihito Sasaki; Agus Setiyono; Ekowati Handharyani; Ibenu Rahmadani; Siswatiana Taha; Sri Adiani; Mawar Subangkit; Hirofumi Sawa; Ichiro Nakamura; Takashi Kimura
  VIROLOGY JOURNAL, 9, 240, 2012年10月, ［査読有り］, ［最終著者, 責任著者］
  英語, 研究論文（学術雑誌）
• Role of JC virus agnoprotein in virion formation
  Tadaki Suzuki; Shingo Semba; Yuji Sunden; Yasuko Orba; Shintaro Kobayashi; Kazuo Nagashima; Takashi Kimura; Hideki Hasegawa; Hirofumi Sawa
  MICROBIOLOGY AND IMMUNOLOGY, 56, 9, 639, 646, 2012年09月, ［査読有り］
  英語, 研究論文（学術雑誌）
• Bilateral Segmental Aplasia with Unilateral Uterine Horn Torsion in a Pomeranian Bitch
  Kensuke Nakamura; Masahiro Yamasaki; Tomohiro Osaki; Hiroshi Ohta; Noboru Sasaki; Keisuke Aoshima; Takashi Kimura; Mitsuyoshi Takiguchi
  JOURNAL OF THE AMERICAN ANIMAL HOSPITAL ASSOCIATION, 48, 5, 327, 330, 2012年09月, ［査読有り］
  英語, 研究論文（学術雑誌）
• Pathological Examination of Lung Tissues in Influenza A Virus-Infected Mice
  Nilton Akio Muto; Yuji Sunden; Tomoe Hattori; Daisuke Fujikura; Yosuke Nakayama; Tadaaki Miyazaki; Mitsuo Maruyama; Takashi Kimura; Hirofumi Sawa
  JAPANESE JOURNAL OF INFECTIOUS DISEASES, 65, 5, 383, 391, 2012年09月, ［査読有り］
  英語, 研究論文（学術雑誌）
• Accumulation of ubiquitinated proteins is related to West Nile virus-induced neuronal apoptosis
  Shintaro Kobayashi; Yasuko Orba; Hiroki Yamaguchi; Takashi Kimura; Hirofumi Sawa
  NEUROPATHOLOGY, 32, 4, 398, 405, 2012年08月, ［査読有り］
  英語, 研究論文（学術雑誌）
• Inhibitory effects of an M2-specific monoclonal antibody on different strains of influenza A virus
  Nilton Akio Muto; Reiko Yoshida; Tadaki Suzuki; Shintaro Kobayashi; Hiroichi Ozaki; Daisuke Fujikura; Rashid Manzoor; Mieko Muramatsu; Ayato Takada; Takashi Kimura; Hirofumi Sawa
  JAPANESE JOURNAL OF VETERINARY RESEARCH, 60, 2-3, 71, 83, 2012年08月, ［査読有り］
  英語, 研究論文（学術雑誌）
• Molecular epidemiology and a loop-mediated isothermal amplification method for diagnosis of infection with rabies virus in Zambia
  Walter Muleya; Boniface Namangala; Aaron Mweene; Luke Zulu; Paul Fandamu; Douglas Banda; Takashi Kimura; Hirofumi Sawa; Akihiro Ishii
  VIRUS RESEARCH, 163, 1, 160, 168, 2012年01月, ［査読有り］
  英語, 研究論文（学術雑誌）
• Single Amino Acid Residue in the A2 Domain of Major Histocompatibility Complex Class I Is Involved in the Efficiency of Equine Herpesvirus-1 Entry
  Michihito Sasaki; Eunmi Kim; Manabu Igarashi; Kimihito Ito; Rie Hasebe; Hideto Fukushi; Hirofumi Sawa; Takashi Kimura
  JOURNAL OF BIOLOGICAL CHEMISTRY, 286, 45, 39370, 39378, 2011年11月, ［査読有り］, ［最終著者, 責任著者］
  英語, 研究論文（学術雑誌）
• ウマMHCクラスI遺伝子導入マウスのウマヘルペスウイルス1型に対する感受性
  木村 享史; 佐々木 道仁; 金 亨振; 福士 秀人; 澤 洋文
  日本獣医学会学術集会講演要旨集, 152回, 184, 184, (公社)日本獣医学会, 2011年08月
  日本語
• Unique heparan sulfate from shrimp heads exhibits a strong inhibitory effect on infections by dengue virus and Japanese encephalitis virus
  Jiancheng Chen; Shuhei Yamada; Yoshiki Hama; Ajaya Kumar Shetty; Takanari Kobayashi; Hiroshi Oda; Kosuke Seiki; Eunmi Kim; Takashi Kimura; Naonori Takahashi; Kazuya I. P. J. Hidari; Takashi Suzuki; Yasuo Suzuki; Kazuyuki Sugahara
  BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, 412, 1, 136, 142, 2011年08月, ［査読有り］
  英語, 研究論文（学術雑誌）
• Paradoxical effects of chondroitin sulfate-E on Japanese encephalitis viral infection
  Eunmi Kim; Megumi Okumura; Hirofumi Sawa; Tadaaki Miyazaki; Daisuke Fujikura; Shuhei Yamada; Kazuyuki Sugahara; Michihito Sasaki; Takashi Kimura
  BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, 409, 4, 717, 722, 2011年06月, ［査読有り］, ［最終著者, 責任著者］
  英語, 研究論文（学術雑誌）
• Detection and characterization of a novel polyomavirus in wild rodents
  Yasuko Orba; Shintaro Kobayashi; Ichiro Nakamura; Akihiro Ishii; Bernard M. Hang'ombe; Aaron S. Mweene; Yuka Thomas; Takashi Kimura; Hirofumi Sawa
  JOURNAL OF GENERAL VIROLOGY, 92, 4, 789, 795, 2011年04月, ［査読有り］
  英語, 研究論文（学術雑誌）
• Equine major histocompatibility complex class I molecules act as entry receptors that bind to equine herpesvirus-1 glycoprotein D
  Michihito Sasaki; Rie Hasebe; Yoshinori Makino; Tadaki Suzuki; Hideto Fukushi; Minoru Okamoto; Kazuya Matsuda; Hiroyuki Taniyama; Hirofumi Sawa; Takashi Kimura
  GENES TO CELLS, 16, 4, 343, 357, 2011年04月, ［査読有り］, ［最終著者, 責任著者］
  英語, 研究論文（学術雑誌）
• Chondroitin sulfate-E induced enhancement of Japanese encephalitis virus infection
  Eunmi Kim; Megumi Okumura; Michihito Sasaki; Daisuke Fujikura; Tadaaki Miyazaki; Hirofumi Sawa; Takashi Kimura
  JOURNAL OF NEUROVIROLOGY, 16, 44, 44, 2010年10月, ［査読有り］, ［最終著者, 責任著者］
  英語
• Flavivirus Encephalitis: Pathological Aspects of Mouse and Other Animal Models
  T. Kimura; M. Sasaki; M. Okumura; E. Kim; H. Sawa
  VETERINARY PATHOLOGY, 47, 5, 806, 818, 2010年09月, ［査読有り］, ［筆頭著者, 責任著者］
  英語, 研究論文（学術雑誌）
• Functional analysis of an alpha-helical antimicrobial peptide derived from a novel mouse defensin-like gene
  Akira Kawaguchi; Tadaki Suzuki; Takashi Kimura; Naoki Sakai; Tokiyoshi Ayabe; Hirofumi Sawa; Hideki Hasegawa
  BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, 398, 4, 778, 784, 2010年08月, ［査読有り］
  英語, 研究論文（学術雑誌）
• Natalizumab Has No Direct Biological Effect on JC Virus Infectivity in Permissive Human Neural Cell Lines
  Tadaki Suzuki; Satoko Yamanouchi; Yuji Sunden; Yasuko Orba; Takashi Kimura; Hirofumi Sawa
  JOURNAL OF MEDICAL VIROLOGY, 82, 7, 1229, 1235, 2010年07月, ［査読有り］
  英語, 研究論文（学術雑誌）
• Transcellular transport of West Nile virus-like particles across human endothelial cells depends on residues 156 and 159 of envelope protein
  Rie Hasebe; Tadaki Suzuki; Yoshinori Makino; Manabu Igarashi; Satoko Yamanouchi; Akihiko Maeda; Motohiro Horiuchi; Hirofumi Sawa; Takashi Kimura
  BMC MICROBIOLOGY, 10, 165, 2010年06月, ［査読有り］
  英語, 研究論文（学術雑誌）
• The Human Polyoma JC Virus Agnoprotein Acts as a Viroporin
  Tadaki Suzuki; Yasuko Orba; Yuki Okada; Yuji Sunden; Takashi Kimura; Shinya Tanaka; Kazuo Nagashima; William W. Hall; Hirofumi Sawa
  PLOS PATHOGENS, 6, 3, e1000801, 2010年03月, ［査読有り］
  英語, 研究論文（学術雑誌）
• Large T Antigen Promotes JC Virus Replication in G(2)-arrested Cells by Inducing ATM- and ATR-mediated G(2) Checkpoint Signaling
  Yasuko Orba; Tadaki Suzuki; Yoshinori Makino; Kanako Kubota; Shinya Tanaka; Takashi Kimura; Hirofumi Sawa
  JOURNAL OF BIOLOGICAL CHEMISTRY, 285, 2, 1544, 1554, 2010年01月, ［査読有り］
  英語, 研究論文（学術雑誌）
• Inhibition of the SDF-1 alpha-CXCR4 axis by the CXCR4 antagonist AMD3100 suppresses the migration of cultured cells from ATL patients and murine lymphoblastoid cells from HTLV-I Tax transgenic mice
  Akira Kawaguchi; Yasuko Orba; Takashi Kimura; Hidekatsu Iha; Masao Ogata; Takahiro Tsuji; Akira Ainai; Tetsutaro Sata; Takashi Okamoto; William W. Hall; Hirofumi Sawa; Hideki Hasegawa
  BLOOD, 114, 14, 2961, 2968, 2009年10月, ［査読有り］
  英語, 研究論文（学術雑誌）
• Infectious entry of equine herpesvirus-1 into host cells through different endocytic pathways
  Rie Hasebe; Michihito Sasaki; Hirofumi Sawa; Ryuichi Wada; Takashi Umemura; Takashi Kimura
  VIROLOGY, 393, 2, 198, 209, 2009年10月, ［査読有り］, ［最終著者, 責任著者］
  英語, 研究論文（学術雑誌）
• Pharmacological cdk inhibitor R-Roscovitine suppresses JC virus proliferation
  Yasuko Orba; Yuji Sunden; Tadaki Suzuki; Kazuo Nagashima; Takashi Kimura; Shinya Tanaka; Hirofumi Sawa
  VIROLOGY, 370, 1, 173, 183, 2008年01月, ［査読有り］
  英語, 研究論文（学術雑誌）
• Cerebellar hypoplasia associated with an avian leukosis virus inducing fowl glioma
  T Toyoda; K Ochiai; H Hatai; M Murakami; E Ono; T Kimura; T Umemura
  VETERINARY PATHOLOGY, 43, 3, 294, 301, 2006年05月, ［査読有り］
  英語, 研究論文（学術雑誌）
• Differential susceptibility of equine and mouse brain microvascular endothelial cells to equine herpesvirus 1 infection
  R Hasebe; T Kimura; K Nakamura; K Ochiai; K Okazaki; R Wada; T Umemura
  ARCHIVES OF VIROLOGY, 151, 4, 775, 786, 2006年04月, ［査読有り］, ［責任著者］
  英語, 研究論文（学術雑誌）
• Efficacy of Intracerebral Immunization against Pseudorabies Virus in Mice
  Shin, J; Sakoda, Y; Kim, J.-H; Tanaka, T; Kida, H; Kimura, T; Ochiai, K; Umemura, T
  Microbiology and Immunology, 50, 823, 830, 2006年
• Efficacy of intracerebral immunization against pseudorabies virus in mice
  Jae-Ho Shin; Yoshihiro Sakoda; Jae Hoon Kim; Tomohisa Tanaka; Hiroshi Kida; Takashi Kimura; Kenji Ochiai; Takashi Umemura
  MICROBIOLOGY AND IMMUNOLOGY, 50, 10, 823, 830, 2006年, ［査読有り］
  英語, 研究論文（学術雑誌）
• Nested polymerase chain reaction for detection of the avian leukosis virus causing so-called fowl glioma
  H Hatai; K Ochiai; Y Tomioka; T Toyoda; K Hayashi; M Anada; M Kato; A Toda; K Ohashi; E Ono; T Kimura; T Umemura
  AVIAN PATHOLOGY, 34, 6, 473, 479, 2005年12月, ［査読有り］
  英語, 研究論文（学術雑誌）
• In vitro demonstration of neural transmission of avian influenza A virus
  K Matsuda; T Shibata; Y Sakoda; H Kida; T Kimura; K Ochiai; T Umemura
  JOURNAL OF GENERAL VIROLOGY, 86, 4, 1131, 1139, 2005年04月, ［査読有り］
  英語, 研究論文（学術雑誌）
• The vagus nerve is one route of transneural invasion for intranasally inoculated influenza A virus in mice
  Matsuda K; Shibata T; Sakoda Y; Kida H; Kimura T; Ochiai K; Umemura T
  Journal of General Virology, 86, 1131, 1139, 2005年04月, ［査読有り］
  英語, 研究論文（学術雑誌）
• Multiple perineuriomas in chicken (Gallus gallus domesticus)
  T Toyoda; K Ochiai; K Ohashi; Y Tomioka; T Kimura; T Umemura
  VETERINARY PATHOLOGY, 42, 2, 176, 183, 2005年03月, ［査読有り］
  英語, 研究論文（学術雑誌）
• Different chemokine expression in lethal and non-lethal murine West Nile virus infection
  K Shirato; T Kimura; T Mizutani; H Kariwa; Takashima, I
  JOURNAL OF MEDICAL VIROLOGY, 74, 3, 507, 513, 2004年11月, ［査読有り］
  英語, 研究論文（学術雑誌）
• Odontogenic cysts in three dogs: One odontogenic keratocyst and two dentigerous cysts
  K Watanabe; T Kadosawa; T Ishiguro; S Takagi; K Ochiai; T Kimura; M Okumura; T Fujinaga
  JOURNAL OF VETERINARY MEDICAL SCIENCE, 66, 9, 1167, 1170, 2004年09月, ［査読有り］
  英語, 研究論文（学術雑誌）
• Genome sequence analysis of the avian retrovirus causing so-called fowl glioma and the promoter activity of the long terminal repeat
  Y Tomioka; K Ochiai; K Ohashi; E Ono; T Toyoda; T Kimura; T Umemura
  JOURNAL OF GENERAL VIROLOGY, 85, 3, 647, 652, 2004年03月, ［査読有り］
  英語, 研究論文（学術雑誌）
• The vagus nerve is one route of transneural invasion for intranasally inoculated influenza A virus in mice
  K Matsuda; CH Park; Y Sunden; T Kimura; K Ochiai; H Kida; T Umemura
  VETERINARY PATHOLOGY, 41, 2, 101, 107, 2004年03月, ［査読有り］
  英語, 研究論文（学術雑誌）
• Nutritional secondary hyperparathyroidism and osteodystrophia fibrosa in a Hodgson's hawk-eagle (Spizaetus nipalensis)
  T Toyoda; K Ochiai; M Komatsu; T Kimura; T Umemura
  AVIAN PATHOLOGY, 33, 1, 9, 12, 2004年02月, ［査読有り］
  英語, 研究論文（学術雑誌）
• Canine ganglioneuroblastoma in the oral mucosa
  K Nakamura; K Ochiai; T Kadosawa; T Kimura; T Umemura
  JOURNAL OF COMPARATIVE PATHOLOGY, 130, 2-3, 205, 208, 2004年02月, ［査読有り］
  英語, 研究論文（学術雑誌）
• Decreased expression of equine herpesvirus-1 early and late genes in the placenta of naturally aborted equine fetuses
  T Kimura; R Hasebe; R Mukaiya; K Ochiai; R Wada; T Umemura
  JOURNAL OF COMPARATIVE PATHOLOGY, 130, 1, 41, 47, 2004年01月, ［査読有り］, ［筆頭著者, 責任著者］
  英語, 研究論文（学術雑誌）
• Persistence of viral RNA segments in the central nervous system of mice after recovery from acute influenza A virus infection
  CH Park; K Matsuda; Y Sunden; A Ninomiya; A Takada; H Ito; T Kimura; K Ochiai; H Kida; T Umemura
  VETERINARY MICROBIOLOGY, 97, 3-4, 259, 268, 2003年12月, ［査読有り］
  英語, 研究論文（学術雑誌）
• In ovo infection with an avian leukosis virus causing fowl glioma: viral distribution and pathogenesis
  Y Tomioka; K Ochiai; K Ohashi; T Kimura; T Umemura
  AVIAN PATHOLOGY, 32, 6, 617, 624, 2003年12月, ［査読有り］
  英語, 研究論文（学術雑誌）
• The effects of antipyretics on influenza virus encephalitis in mice and chicks
  Y Sunden; CH Park; K Matsuda; A Anagawa; T Kimura; K Ochiai; H Kida; T Umemura
  JOURNAL OF VETERINARY MEDICAL SCIENCE, 65, 11, 1185, 1188, 2003年11月, ［査読有り］
  英語, 研究論文（学術雑誌）
• Involvement of the JNK-like protein of the Aedes albopictus mosquito cell line, C6/36, in phagocytosis, endocytosis and infection of West Nile virus
  T Mizutani; M Kobayashi; Y Eshita; K Shirato; T Kimura; Y Ako; H Miyoshi; T Takasaki; Kurane, I; H Kariwa; T Umemura; Takashima, I
  INSECT MOLECULAR BIOLOGY, 12, 5, 491, 499, 2003年10月, ［査読有り］
  英語, 研究論文（学術雑誌）
• Impaired myelinogenesis and early maturation of oligodendrocytes inblack tremor hamster with central nervous system myelin deficiency
  Kim HO; Matsuda K; Kimura T; Ochiai K; Yazawa H; Itakura C; Umemura T
  Journal of Toxicological Pathology, 16, 209, 213, 2003年10月, ［査読有り］
  英語, 研究論文（学術雑誌）
• Sustained hypomyelination and high serum thyroid hormone in aged black tremor hamster
  HO Kim; T Kimura; K Ochiai; H Yazawa; C Itakura; T Umemura
  JAPANESE JOURNAL OF VETERINARY RESEARCH, 51, 2, 113, 120, 2003年08月, ［査読有り］
  英語, 研究論文（学術雑誌）
• Extensive immune-mediated hippocampal damage in mice surviving infection with neuroadapted Sindbis virus
  T Kimura; DE Griffin
  VIROLOGY, 311, 1, 28, 39, 2003年06月, ［査読有り］, ［筆頭著者］
  英語, 研究論文（学術雑誌）
• Passage of equine herpesvirus-1 in suckling mouse brain enhances extraneural virus growth and subsequent hematogenous neuroinvasion
  R Hasebe; T Kimura; K Nakamura; K Okazaki; K Ochiai; R Wada; T Umemura
  JOURNAL OF VETERINARY MEDICAL SCIENCE, 64, 10, 907, 912, 2002年10月, ［査読有り］, ［責任著者］
  英語, 研究論文（学術雑誌）
• Steroid hormones do not reactivate Neospora caninum in ovariectomized mice
  A Kobayashi; S Katagiri; T Kimura; K Ochiai; T Umemura
  JOURNAL OF VETERINARY MEDICAL SCIENCE, 64, 9, 773, 777, 2002年09月, ［査読有り］
  英語, 研究論文（学術雑誌）
• Equine herpesvirus-1-induced encephalomyelitis in mice: a comparative study of neuroadapted virus and its parental strain
  R Hasebe; T Kimura; E Sato; K Okazaki; K Ochiai; R Wada; T Umemura
  JOURNAL OF COMPARATIVE PATHOLOGY, 127, 2-3, 118, 125, 2002年08月, ［査読有り］, ［責任著者］
  英語, 研究論文（学術雑誌）
• The invasion routes of neurovirulent A Hong Kong 483/97 (H5N1) influenza virus into the central nervous system after respiratory infection in mice
  CH Park; M Ishinaka; A Takada; H Kida; T Kimura; K Ochiai; T Umemura
  ARCHIVES OF VIROLOGY, 147, 7, 1425, 1436, 2002年, ［査読有り］
  英語, 研究論文（学術雑誌）
• Distribution of rabbit haemorrhagic disease virus RNA in experimentally infected rabbits
  T Kimura; Mitsui, I; Y Okada; T Furuya; K Ochiai; T Umemura; C Itakura
  JOURNAL OF COMPARATIVE PATHOLOGY, 124, 2-3, 134, 141, 2001年02月, ［査読有り］, ［筆頭著者, 責任著者］
  英語, 研究論文（学術雑誌）
• Role of antibodies in controlling alphavirus infection of neurons
  DE Griffin; S Ubol; P Despres; T Kimura; A Byrnes
  ANTIBODIES IN VIRAL INFECTION, 260, 191, 200, 2001年, ［査読有り］
  英語
• Demonstration of equine herpesvirus-1 gene expression in the placental trophoblasts of naturally aborted equine fetuses
  R Mukaiya; T Kimura; K Ochiai; R Wada; T Umemura
  JOURNAL OF COMPARATIVE PATHOLOGY, 123, 2-3, 119, 125, 2000年08月, ［査読有り］
  英語, 研究論文（学術雑誌）
• The role of CD8(+) T cells and major histocompatibility complex class I expression in the central nervous system of mice infected with neurovirulent Sindbis virus
  T Kimura; DE Griffin
  JOURNAL OF VIROLOGY, 74, 13, 6117, 6125, 2000年07月, ［査読有り］, ［筆頭著者］
  英語, 研究論文（学術雑誌）
• Differences between C57BL/6 and BALB/cBy mice in mortality and virus replication after intranasal infection with neuroadapted Sindbis virus
  DC Thach; T Kimura; DE Griffin
  JOURNAL OF VIROLOGY, 74, 13, 6156, 6161, 2000年07月, ［査読有り］
  英語, 研究論文（学術雑誌）
• Suppressive effects of dominant negative ras mutant N116Y on transformed phenotypes of human bladder cancer cells
  T Watanabe; N Shinohara; A Sazawa; Y Kobayashi; Y Ogiso; T Kimura; M Takiguchi; J Yasuda; A Hashimoto; T Koyanagi; N Kuzumaki
  CANCER LETTERS, 149, 1-2, 195, 202, 2000年02月, ［査読有り］
  英語, 研究論文（学術雑誌）
• Borna disease virus infection in domestic cats: Evaluation by RNA and antibody detection
  Y Nishino; M Funaba; R Fukushima; T Mizutani; T Kimura; R Iizuka; H Hirami; M Hara
  JOURNAL OF VETERINARY MEDICAL SCIENCE, 61, 10, 1167, 1170, 1999年10月, ［査読有り］
  英語, 研究論文（学術雑誌）
• Lead poisoning in wild waterfowl in Japan
  K Ochiai; T Kimura; K Uematsu; T Umemura; C Itakura
  JOURNAL OF WILDLIFE DISEASES, 35, 4, 766, 769, 1999年10月, ［査読有り］
  英語, 研究論文（学術雑誌）
• Borna Disease Virus Infection in Domestic Cats: Evaluation by RNA and Antibody Detection
  Yoshii Nishino; Masayuki Funaba; Ryoko Fukushima; Tetsuya Mizutani; Takashi Kimura; Reiko Iizuka; Hiroshi Hirami; Motonobu Hara
  Journal of Veterinary Medical Science, 61, 10, 1167, 1170, 1999年10月, ［査読有り］
  英語, 研究論文（学術雑誌）
• Canine hemangiopericytoma: an evaluation of metastatic potential
  E Handharyani; K Ochiai; T Kadosawa; T Kimura; T Umemura
  JOURNAL OF VETERINARY DIAGNOSTIC INVESTIGATION, 11, 5, 474, 478, 1999年09月, ［査読有り］
  英語, 研究論文（学術雑誌）
• Complementary DNA cloning, tissue distribution, and synthesis of canine brain natriuretic peptide
  K Asano; M Murakami; D Endo; T Kimura; T Fujinaga
  AMERICAN JOURNAL OF VETERINARY RESEARCH, 60, 7, 860, 864, 1999年07月, ［査読有り］
  英語, 研究論文（学術雑誌）
• Arteriovenous malformation of the cervical spinal cord in a dog
  E Hayashida; K Ochiai; T Kadosawa; T Kimura; T Umemura
  JOURNAL OF COMPARATIVE PATHOLOGY, 121, 1, 71, 76, 1999年07月, ［査読有り］
  英語, 研究論文（学術雑誌）
• Evidence of neoplastic nature and viral aetiology of so-called fowl glioma
  K Ochiai; K Ohashi; T Mukai; T Kimura; T Umemura; C Itakura
  VETERINARY RECORD, 145, 3, 79, 81, 1999年07月, ［査読有り］
  英語, 研究論文（学術雑誌）
• Hepatic lesions in young rabbits experimentally infected with rabbit haemorrhagic disease virus
  D Mikami; JH Park; T Kimura; K Ochiai; C Itakura
  RESEARCH IN VETERINARY SCIENCE, 66, 3, 237, 242, 1999年06月, ［査読有り］
  英語, 研究論文（学術雑誌）
• Neurotoxic effects of 2,5-hexanedione on normal and neurofilament-deficient quail
  T Hirai; M Mizutani; T Kimura; K Ochiai; T Umemura; C Itakura
  TOXICOLOGIC PATHOLOGY, 27, 3, 348, 353, 1999年05月, ［査読有り］
  英語, 研究論文（学術雑誌）
• Single-step reverse transcriptase polymerase chain reaction for detection of Borna disease virus RNA in vitro and in vivo
  T Mizutani; M Ogino; Y Nishino; T Kimura; H Inagaki; D Hayasaka; H Kariwa; Takashima, I
  JAPANESE JOURNAL OF VETERINARY RESEARCH, 46, 4, 165, 169, 1999年02月, ［査読有り］
  英語, 研究論文（学術雑誌）
• A single-tube RT-PCR method for the detection of Borna disease viral genomic RNA
  T Mizutani; M Ogino; Y Nishino; T Kimura; H Kariwa; K Tsujimura; H Inagaki; Takashima, I
  JAPANESE JOURNAL OF VETERINARY RESEARCH, 46, 2-3, 73, 81, 1998年11月, ［査読有り］
  英語, 研究論文（学術雑誌）
• イヌの脳性ナトリウム利尿ペプチド遺伝子のクローニング
  浅野 和之; 村上 正晃; 遠藤 大二; 木村 享史; 奥村 正裕; 廉澤 剛; 藤永 徹
  日本獣医学会学術集会講演要旨集, 125回, 267, 267, (公社)日本獣医学会, 1998年03月
  日本語
• Gizzard adenocarcinoma in an aged Humboldt penguin (Spheniscus humboldti)
  KO Cho; T Kimura; K Ochiai; C Itakura
  AVIAN PATHOLOGY, 27, 1, 100, 102, 1998年02月, ［査読有り］
  英語, 研究論文（学術雑誌）
• Bronchiolar-alveolar carcinoma in a cow
  Y Okada; K Ochiai; K Osaki; T Kimura; C Itakura
  JOURNAL OF COMPARATIVE PATHOLOGY, 118, 1, 69, 74, 1998年01月, ［査読有り］
  英語, 研究論文（学術雑誌）
• Significance of Marek's disease virus serotype 1-specific phosphorylated proteins in Marek's disease skin lesions
  KO Cho; D Endoh; T Kimura; K Ochiai; C Itakura
  AVIAN PATHOLOGY, 26, 4, 707, 720, 1997年12月, ［査読有り］
  英語, 研究論文（学術雑誌）
• Apocrine gland tumor of the eyelid in a dog
  T Hirai; M Mubarak; T Kimura; K Ochiai; C Itakura
  VETERINARY PATHOLOGY, 34, 3, 232, 234, 1997年05月, ［査読有り］
  英語, 研究論文（学術雑誌）
• 静岡県における兎出血病の発生．
  伊藤謙一; 川嶋和晴; 大庭芳和; 播谷亮; 木村享史; 板倉智敏
  日本獣医師会雑誌, 50, 9, 523, 526, 日本獸医師会, 1997年, ［査読有り］
  日本語, 研究論文（学術雑誌）, 岡県の一観光牧場で, 9日間に成兎60羽中53羽 (88.3%) が沈うつ症状を示して発症後数時間で死亡し, 死亡3例について病理学的に検索したところ, 兎出血病 (Rabbit hemorrhagic disease: RHD) に特微的な病変が認められた. すなわち, 組織学的に壊死性肝炎, 肺・腎臓における播種性血管内凝固が認められ, 抗RHDウィルスIgGによる免疫染色で肝細胞に陽性反応が認められた. また, 電子顕微鏡学的には, 壊死肝細胞細胞質にカリシウイルス様粒子が観察された. 死亡例の肝臓乳剤を接種された2羽の兎で本病の再現がなされ, 肝臓からカリシウイルス粒子が精製された. 今回の例は1994年 (北海道) に続いてわが国における第2件目であった.
• Inherited muscular disorder in mutant Japanese quail (Coturnix coturnix japonica): An immunohistochemical study
  S Tanaka; IS Braga; T Kimura; K Ochiai; C Itakura; M Mizutani
  JOURNAL OF COMPARATIVE PATHOLOGY, 115, 2, 139, 150, 1996年08月, ［査読有り］
  英語, 研究論文（学術雑誌）
• Sequential skin lesions in chickens experimentally infected with Marek's disease virus
  KO Cho; M Mubarak; T Kimura; K Ochiai; C Itakura
  AVIAN PATHOLOGY, 25, 2, 325, 343, 1996年06月, ［査読有り］
  英語, 研究論文（学術雑誌）
• Inherited muscular disorder in mutant Japanese quail (Coturnix coturnix japonica): An ultrastructural study
  S Tanaka; IS Braga; T Kimura; K Ochiai; C Itakura; M Mizutani
  JOURNAL OF COMPARATIVE PATHOLOGY, 114, 3, 325, 337, 1996年04月, ［査読有り］
  英語, 研究論文（学術雑誌）
• INHERITED MUSCULAR DISORDER IN MUTANT JAPANESE-QUAIL (COTURNIX-COTURNIX-JAPONICA) - RELATIONSHIP BETWEEN THE DEVELOPMENT OF MUSCLE LESIONS AND AGE
  IS BRAGA; S TANAKA; T KIMURA; C ITAKURA; M MIZUTANI
  JOURNAL OF COMPARATIVE PATHOLOGY, 113, 2, 131, 143, 1995年08月, ［査読有り］
  英語, 研究論文（学術雑誌）
• ANALYSIS OF VIRUS-CELL BINDING CHARACTERISTICS ON THE DETERMINATION OF JAPANESE ENCEPHALITIS-VIRUS SUSCEPTIBILITY
  T KIMURA; J KIMURAKURODA; K NAGASHIMA; K YASUI
  ARCHIVES OF VIROLOGY, 139, 3-4, 239, 251, 1994年, ［査読有り］, ［筆頭著者］
  英語, 研究論文（学術雑誌）
• キスカル酸レセプター刺激によるイノシトールリン脂質代謝応答の加齢ラット海馬での増大．
  斎藤巨志; 中川勇三; 石原高文; 木村享史; 長嶋和郎
  神経化学, 29, 472, 473, 1990年, ［査読有り］
  日本語, 研究論文（その他学術会議資料等）

• 非臨床モデルでのバロキサビル マルボキシル投与経路の検討~ヤンバルクイナにおける吸収性改善を目指して~
  三木万梨子; 島津陽; 尾原涼; 大崎裕美; 宍戸貴雄; 池中良徳; 木村享史; 日尾野隆大; 日尾野隆大; 磯田典和; 磯田典和; 迫田義博; 迫田義博, 日本野生動物医学会大会・講演要旨集, 30th, 2024年
• イヌ血管肉腫におけるヒストンラクチル化の役割および代謝の特徴の解析
  鈴木玲海; 青島圭佑; 山崎淳平; 平島一輝; 木村享史, 日本癌学会学術総会抄録集(Web), 83rd, 2024年
• イヌ血管肉腫におけるヒストンラクチル化とグルタミン代謝の役割の解析
  鈴木玲海; 青島圭佑; 山崎淳平; 安井博宣; 平島一輝; 木村享史, がんと代謝研究会プログラム&抄録集, 9th, 2023年
• イヌ血管肉腫におけるDNAメチル化異常とDNAメチル化阻害による抗腫瘍効果
  鹿又崚; 青島圭佑; 青島圭佑; 鈴木玲海; 山崎淳平; 山崎淳平; 木村享史, 日本獣医学会学術集会講演要旨集, 166th, 2023年
• イヌ血管肉腫におけるヒストンラクチル化およびグルタミン代謝の役割の解析
  鈴木玲海; 青島圭佑; 山崎淳平; 安井博宣; 平島一輝; 木村享史, 日本癌学会学術総会抄録集(Web), 82nd, 2023年
• 鼻疽菌検出のための新規dry LAMP法の開発
  中瀬満; THAPA Jeewan; BATBAATAR Vanaabaatar; KHURTSBAATAR Ochirbat; ENKHTUUL Batchuluun; UNENBAT Jugderkhorloo; 中島千絵; 鈴木定彦; 木村享史, 日本獣医学会学術集会講演要旨集, 166th, 2023年
• バロキサビルマルボキシルのニワトリへの4週間反復経口投与による安全性評価
  三木 万梨子; 尾原 涼; 西村 享平; 岡 良子; 宍戸 貴雄; 福島 民雄; 吉本 淳; 中山 翔太; 木村 享史; 池中 良徳; 日尾野 隆大; 磯田 典和; 迫田 義博, 日本獣医学会学術集会講演要旨集, 165回, [DV1A, 08], 2022年09月
  (公社)日本獣医学会, 日本語
• キタキツネ及びタヌキからの高病原性鳥インフルエンザウイルスの分離
  日尾野 隆大; 磯田 典和; 小林 篤史; 小林 大樹; 鈴木 玲海; 佐竹 優樹; 松野 啓太; 佐鹿 万里子; 伴 日向子; 小林 茉弥; 高谷 文仁; 冨士田 裕子; 木村 享史; 迫田 義博, 日本獣医学会学術集会講演要旨集, 165回, [DV1A, 09], 2022年09月
  (公社)日本獣医学会, 日本語
• 高病原性鳥インフルエンザウイルスに感染したキタキツネの病理学的解析とウイルス受容体の検出
  小林 大樹; 小林 篤史; 日尾野 隆大; 原田 里桜; 鈴木 玲海; 松野 啓太; 磯田 典和; 高谷 文仁; 冨士田 裕子; 木村 享史; 迫田 義博, 日本獣医学会学術集会講演要旨集, 165回, [DV1A, 10], 2022年09月
  (公社)日本獣医学会, 日本語
• Burkholderia thailandensis感染マクロファージ細胞株RAW264におけるパイロトーシスに対するCOX-2の影響
  市川世識; 青島圭佑; 小林篤史; 木村享史, 日本獣医学会学術集会講演要旨集, 164th (CD-ROM), 2021年
• ヒストン脱アセチル化酵素阻害剤およびブロモドメイン阻害剤はイヌ血管肉腫細胞株に細胞死を誘導する
  鈴木玲海; 青島圭佑; 小林篤史; 木村享史, 日本獣医学会学術集会講演要旨集, 164th (CD-ROM), 2021年
• 獣医病理学研修会出題標本 No.1248.コウジョウセンガゼルの肺(北海道大学)
  木村享史; ERDEMSURAKH Ochbayar; 青島圭佑; 小林篤史, 日本獣医学会学術集会講演要旨集, 163rd, 2020年
• 鉛散弾の経口投与によるバルバリーガモの鉛の血中濃度の経時変化および体内分布の解析
  佐藤裕; 石井千尋; 中山翔太; 一瀬貴大; 齊藤慶輔; 渡邊有希子; 小笠原浩平; 鳥本亮太; 小林篤史; 木村享史; 池中良徳; 石塚真由美, 日本獣医学会学術集会講演要旨集, 162nd, 504, 2019年08月20日
  日本語
• ラット由来細胞株Rn33Bの神経分化はEHV-1感受性を低下させる
  港江利奈; 青島圭佑; 小林篤史; 木村享史, 日本ウイルス学会学術集会プログラム・予稿集(Web), 67th, 2019年
• ドキソルビシン耐性イヌ血管肉腫細胞株の樹立と薬剤耐性機構の解析
  森田 敦也; 青島 圭佑; 小林 篤史; 木村 享史, 日本獣医学会学術集会講演要旨集, 161回, 303, 303, 2018年08月
  (公社)日本獣医学会, 日本語
• イヌ血管肉腫におけるCXCR7シグナル伝達機構の解析
  大西 慎一; 青島 圭佑; 小林 篤史; 木村 享史, 日本獣医学会学術集会講演要旨集, 160回, 321, 321, 2017年08月
  (公社)日本獣医学会, 日本語
• ウマ主要組織適合遺伝子複合体クラスI遺伝子導入マウスのウマヘルペスウイルス1型に対する感受性の検討
  港 江利奈; 青島 圭佑; 小林 篤史; 木村 享史, 日本獣医学会学術集会講演要旨集, 159回, 319, 319, 2016年08月
  (公社)日本獣医学会, 日本語
• 北大農場で発生したリステリア症罹患羊の飼育環境からのリステリア属菌の分離とゲノム解析
  長谷部 理絵; 青島 圭佑; 棟居 佳子; 三谷 朋弘; 平井 佑治; 山崎 剛士; 木村 享史; 堀田 基広, 日本獣医学会学術集会講演要旨集, 159回, 418, 418, 2016年08月
  (公社)日本獣医学会, 日本語
• 2010年に稚内で分離された2株の高病原性鳥インフルエンザウイルスの病原性比較
  直亨則; 梶原将大; 丸山隼輝; 木村享史; MANZOOR Rashid; 村松美笑子; 岡松正敏; 宮本洋子; 吉田玲子; 迫田義博; 喜田宏; 高田礼人, 日本ウイルス学会学術集会プログラム・抄録集, 61st, 150, 2013年10月29日
  日本語
• 超音波検査により診断が可能であった子宮捻転の犬の1例
  中村 健介; 山崎 真大; 大田 寛; 森下 啓太郎; 木村 享史; 滝口 満喜, 日本獣医画像診断学会抄録, 54回, 28, 28, 2013年09月
  日本獣医画像診断学会, 日本語
• ラット中脳由来神経細胞株CSM14.1における日本脳炎ウイルス感染様式
  木村享史; 奥村恵; 金恩美; 佐々木道仁; 大場靖子; 澤洋文, 日本獣医学会学術集会講演要旨集, 156th, 2013年
• オートファジーはウエストナイルウイルスの増殖を抑制する
  小林進太郎; 大場靖子; 山口宏樹; 佐々木道仁; 長谷部理絵; 木村享史; 澤洋文, 日本ウイルス学会学術集会プログラム・抄録集, 61st, 2013年
• 霊長類動物からの新規ポリオーマウイルスの検出
  山口宏樹; 小林進太郎; 石井秋宏; 小川寛人; 木村享史; 澤洋文; 大場靖子, 日本分子生物学会年会プログラム・要旨集(Web), 36th, 2013年
• インフルエンザウイルス感染におけるマウス肺の病理学的変化の観察
  澤洋文; MUTO Mton‐Akio; 寸田祐嗣; 服部ともえ; 藤倉大輔; 中山洋佑; 宮崎忠昭; 丸山光生; 木村享史, 日本ウイルス学会学術集会プログラム・抄録集, 60th, 334, 2012年10月31日
  日本語
• ザンビアの野生動物におけるオルソポックスウイルス感染の疫学調査
  大場靖子; 石井秋宏; トーマス 由佳; 小川寛人; 中村一郎; 木村享史; 森川茂; 西條政幸; 澤洋文, 日本ウイルス学会学術集会プログラム・抄録集, 60th, 443, 2012年10月31日
  日本語
• 両側性子宮分節性無形成から片側性子宮角捻転に至った犬の1例
  横山望; 中村健介; 木村享史; 大田寛; 山崎真大; 滝口満喜, 北海道獣医師会雑誌, 56, 8, 418, 418, 2012年08月10日
  (公社)北海道獣医師会, 日本語
• ウエストナイルウイルス感染神経細胞におけるユビキチン化タンパク質の蓄積
  小林進太郎; 小林進太郎; 大場靖子; 山口宏樹; 木村享史; 澤洋文; 澤洋文, 日本ウイルス学会学術集会プログラム・抄録集, 60th, 2012年
• 霊長類動物におけるパラインフルエンザウイルスの疫学調査
  佐々木道仁; 石井秋宏; 大場靖子; トーマス由佳; 小川寛人; 中村一郎; 木村享史; 澤洋文; 澤洋文, 日本ウイルス学会学術集会プログラム・抄録集, 60th, 2012年
• ザンビアにおける霊長類動物からの新規ポリオーマウイルスの検出
  山口宏樹; 山口宏樹; 大場靖子; 小林進太郎; 小林進太郎; 石井秋宏; 小川寛人; 中村一郎; THOMAS由佳; 木村享史; 澤洋文; 澤洋文, 日本ウイルス学会学術集会プログラム・抄録集, 60th, 2012年
• 霊長類動物におけるパラインフルエンザウイルス3型の疫学調査
  佐々木道仁; 石井秋宏; 大場靖子; THOMAS Yuka; 小川寛人; 中村一郎; 木村享史; 澤洋文; 澤洋文, 日本分子生物学会年会プログラム・要旨集(Web), 35th, 2012年
• ウマMHC class Iが示すウマヘルペスウイルス1型レセプター機能の解析
  佐々木道仁; 五十嵐学; 澤洋文; 伊藤公人; 福士秀人; 木村享史, 日本獣医学会学術集会講演要旨集, 152nd, 239, 239, 2011年08月31日
  (公社)日本獣医学会, 日本語
• ザンビア共和国の霊長類動物におけるポリオーマウイルスの疫学調査
  山口宏樹; 小林進太郎; 大場靖子; 石井秋宏; 小川寛人; Thomas由佳; 木村享史; 澤洋文, 日本獣医学会学術集会講演要旨集, 152nd, 2011年
• 野生齧歯動物からの新規ポリオーマウイルスの検出
  大場靖子; 小林進太郎; 中村一郎; 石井秋宏; 木村享史; 澤洋文, 日本ウイルス学会学術集会プログラム・抄録集, 58th, 445, 2010年10月15日
  日本語
• Disruption of Intracellular Vesicular Trafficking by Agnoprotein is Essential for Viroporin Activity and JC Virus Replication
  Tadaki Suzuki; Yasuko Orba; Yoshinori Malcino; Yuki Okada; Yuji Sunden; Takashi Kimura; Hideki Hasegawa; Tetsutaro Sata; William W. Hall; Hirofumi Sawa, JOURNAL OF NEUROVIROLOGY, 16, 84, 84, 2010年10月
  英語, 研究発表ペーパー・要旨（国際会議）
• Large T antigen promotes JC virus replication in G2 arrest by inducing G2 checkpoint signaling
  Yasuko Orba; Tadaki Suzuki; Takashi Kimura; Hirofumi Sawa, JOURNAL OF NEUROVIROLOGY, 16, 64, 65, 2010年10月
  英語, 研究発表ペーパー・要旨（国際会議）
• Cys80 of JC Virus Capsid Protein, VP1 is Essential for Intrapentamer Disulfide Bond and Pentamer Formation
  Shintaro Kobayashi; Tadaki Suzuki; Manabu Igarashi; Noriko Ohtake; Keita Nagakawa; Kimihito Ito; Kenichi Niikura; Takashi Kimura; Harumi Kasamatsu; Hirofumi Sawa, JOURNAL OF NEUROVIROLOGY, 16, 45, 46, 2010年10月
  英語, 研究発表ペーパー・要旨（国際会議）
• 新規エントリーレセプターを介したウマヘルペスウイルス1型の細胞内侵入機構の解析
  佐々木道仁; 長谷部理絵; 福士秀人; 谷山弘行; 澤洋文; 木村享史, 日本獣医学会学術集会講演要旨集, 150th, 2010年
• Inhibition of the SDF-1F?-CXCR4 Axis by the CXCR4 Antagonist AMD3100 Suppresses the Migration of Human ATLL Cells and Murine Lymphoblastoid Cells from HTLV-I Tax Transgenic Mice
  A. Kawaguichi; Hidekatsu, I; H. Hasegawa; H. Sawa; M. Ogata; T. Tsuji; T. Kimura; T. Sata; W. W. Hall; Y. Orba, AIDS RESEARCH AND HUMAN RETROVIRUSES, 25, 11, 1212, 1212, 2009年11月
  英語, 研究発表ペーパー・要旨（国際会議）
• CXCR4アンタゴニスト(AMD3100)を用いたSCIDマウスにおけるTaxトランスジェニックマウス由来腫瘍細胞の組織浸潤抑制
  川口晶; 辻隆裕; 大場靖子; 木村享史; 相内章; 伊波英克; 緒方正男; 佐多徹太郎; 澤洋文; 長谷川秀樹, 日本ウイルス学会学術集会プログラム・抄録集, 57th, 445, 2009年10月01日
  日本語
• ラット神経由来CSM14.1細胞株における日本脳炎ウイルス感受性
  奥村恵; 木村享史; 大場靖子; 大場靖子; 澤洋文; 澤洋文, 日本ウイルス学会学術集会プログラム・抄録集, 57th, 2009年
• Viroporin activity of JCV agnoprotein
  Tadaki Suzuki; Yasuko Orba; Yuji Sunden; Takashi Kimura; Hirofumi Sawa, JOURNAL OF NEUROVIROLOGY, 15, 96, 97, 2009年
  英語, 研究発表ペーパー・要旨（国際会議）
• ヒトATL細胞及びTaxトランスジェニックマウス由来腫瘍細胞のSDF‐1αに対する走化性
  川口晶; 大場靖子; 木村享史; 伊波英克; 緒方正男; 辻隆裕; 佐多徹太郎; 澤洋文; 長谷川秀樹, 日本ウイルス学会学術集会プログラム・抄録集, 56th, 247, 2008年10月01日
  日本語
• 気胸を併発した先天性肺葉性肺気腫の犬の1例
  上條弘美; 高木哲; 大田寛; 山崎真大; 木村享史; 滝口満喜, 北海道獣医師会雑誌, 52, 8, 420, 420, 2008年08月01日
  (公社)北海道獣医師会, 日本語
• ATL腫瘍細胞の走化性におけるCXCR4を介したシグナル経路の解析
  川口晶; 大場靖子; 木村享史; 伊波英克; 緒方正男; 佐多徹太郎; 澤洋文; 長谷川秀樹, 補体シンポジウム講演集, 45th, 179, 2008年07月
  日本語
• JC virus agnoprotein modifies plasma membrane permeability and facilitates
  Tadaki Suzuki; Yuki Okada; Yasuko Orba; Yuji Sunden; Takashi Kimura; Kazuo Nagashima; Hirofumi Sawa, JOURNAL OF NEUROVIROLOGY, 13, 128, 128, 2007年
  英語, 研究発表ペーパー・要旨（国際会議）
• Pharmacological cdk inhibitor suppresses JC virus proliferation
  Yasuko Orba; Yuji Sunden; Tadaki Suzuki; Takashi Kimura; Shinya Tanaka; Kazuo Nagashima; Hirofumi Sawa, JOURNAL OF NEUROVIROLOGY, 13, 109, 110, 2007年
  英語, 研究発表ペーパー・要旨（国際会議）
• Biological effects of Natalizurnab on JC virus infectivity in its permissive human neural cell lines in vitro
  Tadaki Suzuki; Satoko Yamanouchi; Yuji Sunden; Yasuko Orba; Shinya Tanaka; Takashi Kimura; Hirofumi Sawa, JOURNAL OF NEUROVIROLOGY, 13, 127, 127, 2007年
  英語, 研究発表ペーパー・要旨（国際会議）
• Visualization of West Nile virus particles for examination on the cellular entry mechanism
  Yoshinori Makino; Tadaki Suzuki; Rie Hasebe; Akihiko Maeda; Hidehiro Takahashi; Takashi Kimura; Hirofumi Sawa, JOURNAL OF NEUROVIROLOGY, 13, 100, 100, 2007年
  英語, 研究発表ペーパー・要旨（国際会議）
• Efficacy of intracerebral vaccination against pseudorabies virus in mice
  Jae-Ho Shin; Yoshihiro Sakoda; Jae Hoon Kim; Tomohisa Tanaka; Hiroshi Kida; Takashi Kimura; Kenji Ochiai; Takashi Umemura, JOURNAL OF NEUROIMMUNOLOGY, 178, 114, 114, 2006年09月
  英語, 研究発表ペーパー・要旨（国際会議）
• スリランカ津波被災地ならびにその近郊に生息する野生げっ歯類の病理学的検査
  木村享史; 沢洋文; 片倉賢; 中村一郎; 有川二郎; 松本芳嗣; RAJAPAKSE R.P.V.Jayanthe; 高島郁夫; 梅村孝司, 日本獣医学会学術集会講演要旨集, 140th, 72, 72, 2005年08月31日
  (公社)日本獣医学会, 日本語
• ホジキン型リンパ腫が疑われた猫の1例
  岡崎和子; 滝口満喜; 木村享史; 松田英一郎; 稲葉睦, 北海道獣医師会雑誌, 48, 8, 319, 319, 2004年08月01日
  (公社)北海道獣医師会, 日本語
• 超音波検査によりしん出性収縮性心膜炎と診断された犬の1例
  浜本耕平; 滝口満喜; 伊藤啓; 木村享史; 廉沢剛; 稲葉睦, 北海道獣医師会雑誌, 47, 8, 315, 315, 2003年08月01日
  (公社)北海道獣医師会, 日本語
• 神経症状を呈するネコにおけるボルナ病ウイルス感染の診断と病体の調査
  西野 佳以; 吉田 倫子; 田所 真弓; 栗田 吾郎; 辻本 元; 奥村 正裕; 木村 享史; 水谷 哲也, 日本獣医学会学術集会講演要旨集, 129回, 81, 81, 2000年03月
  (公社)日本獣医学会, 日本語
• 日本で発生した兎出血病由来ウイルスを用いての実験病理学的研究
  三井 一鬼, 日本獣医学会学術集会講演要旨集, 123回, 96, 96, 1997年03月
  (公社)日本獣医学会, 日本語

• 法獣医学と法科学
  石塚真由美; 川本恵子; 佐伯潤; 田口本光; 田中亜紀; 内田和幸; 梅谷綾子; 木村享史; 鈴木良; 高橋真吾; 町家奈; 松本周; 三上正隆; 日本法獣医学会, 第4章 動物遺伝学的証拠とDNA解析;第11章 法獣医骨学
  Jason H. Byrd; Patricia Norris; Nancy Bradley-Siemens, 学窓社, 2024年09月, 9784873627953, xxvii, 567p, 日本語, ［共訳］
• 動物病理学総論第4版
  木村享史, 第8章 免疫病理
  文永堂出版, 2023年03月, 9784830032851, xv, 299p, 日本語, ［共編者(共編著者)］
• 動物病理学各論第3版
  木村享史, 第1章心臓P1-16; 第3章体腔P78-81
  文永堂出版, 2021年03月, 9784830032806, xv, 509p, 日本語, ［共編者(共編著者)］
• 動物病理カラーアトラス第2版
  木村享史, 第1編Ⅲ心内膜の病変P4；心筋の病変P10-11；第5編Ⅱ肝臓の病変P142
  文永堂出版, 2018年01月, 9784830032684, xvii, 320p, 日本語, ［共編者(共編著者)］
• 動物病理学総論第3版．日本獣医病理学会編
  木村 享史, 第7章第4節 炎症のメディエーター p.129-135，第7章第6節第3項 肉芽腫性炎症に分類される疾患p.148-152
  文永堂出版, 2013年04月, ［分担執筆］
• 動物病理学各論第2版．日本獣医病理学会編．
  木村 享史, 第1章第2節第4項 リンパ管 p.26-27，第1章第2節第5項 血管およびリンパ管の腫瘍p.28-29，第3章第2節 腹腔，腹膜 p.77-81
  文永堂出版, 2010年03月, ［分担執筆］
• 新獣医学辞典．新獣医学辞典編集委員会編．
  木村 享史, 壊死後性肝硬変 p.122，間質性肺炎 p.238，奇異性塞栓症 p.259，クロイツフェルト‐ヤコブ病 p.340
  チクサン出版社, 2008年01月, ［分担執筆］
• 動物病理カラーアトラス．日本獣医病理学会編．
  木村 享史, 第5編 消化器系Ⅱ 5-8. 兎出血病 p.115
  文永堂出版, 2007年02月, ［分担執筆］

• バロキサビルマルボキシルのニワトリへの4週間反復経口投与による安全性評価
  三木 万梨子; 尾原 涼; 西村 享平; 岡 良子; 宍戸 貴雄; 福島 民雄; 吉本 淳; 中山 翔太; 木村 享史; 池中 良徳; 日尾野 隆大; 磯田 典和; 迫田 義博
  日本獣医学会学術集会講演要旨集, 2022年09月, (公社)日本獣医学会, 日本語
  2022年09月 - 2022年09月
• キタキツネ及びタヌキからの高病原性鳥インフルエンザウイルスの分離
  日尾野 隆大; 磯田 典和; 小林 篤史; 小林 大樹; 鈴木 玲海; 佐竹 優樹; 松野 啓太; 佐鹿 万里子; 伴 日向子; 小林 茉弥; 高谷 文仁; 冨士田 裕子; 木村 享史; 迫田 義博
  日本獣医学会学術集会講演要旨集, 2022年09月, (公社)日本獣医学会, 日本語
  2022年09月 - 2022年09月
• 高病原性鳥インフルエンザウイルスに感染したキタキツネの病理学的解析とウイルス受容体の検出
  小林 大樹; 小林 篤史; 日尾野 隆大; 原田 里桜; 鈴木 玲海; 松野 啓太; 磯田 典和; 高谷 文仁; 冨士田 裕子; 木村 享史; 迫田 義博
  日本獣医学会学術集会講演要旨集, 2022年09月, (公社)日本獣医学会, 日本語
  2022年09月 - 2022年09月
• 鼻疽の診断抗原の探索
  市川 世識; 飯沼 由希帆; 岡川 朋弘; 前川 直也; 村田 史郎; 今内 覚; 木下 優太; 丹羽 秀和; 青島 圭佑; 小林 篤史; 大橋 和彦; 木村 享史
  日本獣医学会学術集会講演要旨集, 2022年09月, (公社)日本獣医学会, 日本語
  2022年09月 - 2022年09月
• 鼻疽の診断抗原の探索
  市川 世識; 飯沼 由希帆; 岡川 朋弘; 前川 直也; 村田 史郎; 今内 覚; 木下 優太; 丹羽 秀和; 青島 圭佑; 小林 篤史; 大橋 和彦; 木村 享史
  日本獣医学会学術集会講演要旨集, 2022年09月, (公社)日本獣医学会, 日本語
  2022年09月 - 2022年09月
• ヒストンアセチル化の改変はイヌ血管肉腫細胞に抗腫瘍効果をもたらす
  鈴木 玲海; 青島 圭佑; 山崎 淳平; 小林 篤史; 木村 享史
  日本獣医学会学術集会講演要旨集, 2022年09月, (公社)日本獣医学会, 日本語
  2022年09月 - 2022年09月
• ラット中脳由来神経細胞株CSM14.1における日本脳炎ウイルス感染様式
  木村 享史; 奥村 恵; 金 恩美; 佐々木 道仁; 大場 靖子; 澤 洋文
  日本獣医学会学術集会講演要旨集, 2013年08月, (公社)日本獣医学会, 日本語
  2013年08月 - 2013年08月
• オートファジーによるウエストナイルウイルス増殖抑制機構の解明
  小林 進太郎; 大場 靖子; 山口 宏樹; 佐々木 道仁; 長谷部 理絵; 木村 享史; 澤 洋文
  日本獣医学会学術集会講演要旨集, 2013年08月, (公社)日本獣医学会, 日本語
  2013年08月 - 2013年08月
• インドネシア共和国に生息するオオコウモリから分離した新規ヘルペスウイルスの性状解析
  佐々木 道仁; Agus Setiyono; Ekowati Handharyani; 中村 一郎; 澤 洋文; 木村 享史
  日本獣医学会学術集会講演要旨集, 2013年08月, (公社)日本獣医学会, 日本語
  2013年08月 - 2013年08月
• ウイルス感染と免疫
  木村 享史
  日本獣医病理学会スライドセミナー“炎症と免疫”, 2013年03月30日, 日本語, 公開講演，セミナー，チュートリアル，講習，講義等
  東京大学, ［招待講演］, ［国内会議］
• Seminar Public Awareness “Surveillance of Potential Pathogens in Fruitbats in Indonesia”
  Takashi Kimura
  Joint Seminar between National Committee on Zoonosis and Bogor Agricultural University, 2013年03月09日, 英語, 公開講演，セミナー，チュートリアル，講習，講義等
  IPB International Convention Center, Bogor, Indonesia, ［招待講演］
• MHC class I を介したウマヘルペスウイルス1型の細胞内侵入機構
  木村 享史
  第６回獣医学科特別セミナー, 2011年08月04日, 日本語, 公開講演，セミナー，チュートリアル，講習，講義等
  山口大学, ［招待講演］
• ウマMHCクラスI遺伝子導入マウスのウマヘルペスウイルス1型に対する感受性
  木村 享史; 佐々木 道仁; 金 亨振; 福士 秀人; 澤 洋文
  日本獣医学会学術集会講演要旨集, 2011年08月, (公社)日本獣医学会, 日本語
  2011年08月 - 2011年08月
• 犬末梢血単核球におけるCD56mRNA発現とその定量法の確立
  星野 有希; 高木 哲; 木村 享史; 奥村 正裕; 藤永 徹
  日本獣医学会学術集会講演要旨集, 2007年03月, (公社)日本獣医学会, 日本語
  2007年03月 - 2007年03月
• トリの神経膠腫原因ウイルス接種鶏に見られた小脳異形成
  豊田 武士; 落合 謙爾; 畑井 仁; 村上 真理子; 木村 享史; 梅村 孝司
  日本獣医学会学術集会講演要旨集, 2005年03月, (公社)日本獣医学会, 日本語
  2005年03月 - 2005年03月
• Ｈ５強毒インフルエンザウイルスの神経病原性と解熱剤投与の影響に関する実験的研究
  梅村孝司; 松田一哉; 朴天鍋; 寸田祐嗣; 木村享史; 落合謙爾; 喜田宏
  日本病理学会会誌, 2004年04月, 日本語
  2004年04月 - 2004年04月
• Immune responses to Sindbis virus infection determine the outcome of acute encephalitis in mice.
  Takashi Kimura
  Joint Symposium between Hokkaido University Graduate School of Veterinary Medicine and Seoul National University College of Veterinary Medicine-Second COE International Symposium for Zoonosis Control-, 2003年12月05日, 英語, シンポジウム・ワークショップパネル（指名）
  Seoul National University, Korea
• 中枢神経系におけるウイルス感染の免疫学的制御
  木村 享史
  2003年度第5回生物研セミナー, 2003年11月21日, 日本語, 公開講演，セミナー，チュートリアル，講習，講義等
  麻布大学, ［招待講演］
• イヌの脳性ナトリウム利尿ペプチド遺伝子のクローニング
  浅野 和之; 村上 正晃; 遠藤 大二; 木村 享史; 奥村 正裕; 廉澤 剛; 藤永 徹
  日本獣医学会学術集会講演要旨集, 1998年03月, (公社)日本獣医学会, 日本語
  1998年03月 - 1998年03月

• 総合獣医療実習, 2024年, 学士課程, 獣医学部
• 臨床疾病学特論, 2024年, 博士後期課程, 獣医学院
• 獣医科学特別研究, 2024年, 博士後期課程, 獣医学院
• 獣医病理学特論, 2024年, 博士後期課程, 獣医学院
• 獣医科学特論演習, 2024年, 博士後期課程, 獣医学院
• 一般教育演習(ﾌﾚｯｼｭﾏﾝｾﾐﾅｰ), 2024年, 学士課程, 全学教育
• 泌尿器病理学, 2024年, 学士課程, 獣医学部
• 神経・運動器病理学, 2024年, 学士課程, 獣医学部
• アドバンスト演習, 2024年, 学士課程, 獣医学部
• 病理学総論, 2024年, 学士課程, 獣医学部
• 消化器病理学, 2024年, 学士課程, 獣医学部
• 総合獣医療実習, 2024年, 学士課程, 獣医学部
• 循環器・呼吸器病理学, 2024年, 学士課程, 獣医学部

• 日本獣医病理学専門家協会
• 日本ウイルス学会
• American Society for Virology
• 日本獣医学会

• ウマヘルペスウイルス1型感染神経細胞におけるウイルス遺伝子発現制御機構の解明
  科学研究費助成事業
  2022年04月01日 - 2026年03月31日
  木村 享史; 青島 圭佑
  ウマヘルペスウイルス1型 (EHV-1) は神経細胞へ潜伏感染することが知られており、その成立にはウイルス遺伝子の発現抑制が関与すると推測されるが、詳細は不明である。本研究では、未分化状態においてEHV-1に高い感受性を示すが神経分化によって著しく感受性が低下するラット脳由来細胞株Rn33B-A68B2Mを潜伏感染モデルとして用い、神経分化状態と未分化状態におけるEHV-1増殖性の相違を規定する分子機構を解明し、神経細胞におけるEHV-1潜伏感染の成立機序について考察を行うことを目的とする。
  令和5年度はORF63（ICP0遺伝子）の3'非翻訳領域を認識するmiRNAの同定を試みた。ORF63の読み取り枠直後から3'方向へ向かう193 bpのEHV-1ゲノムDNA断片をpmirGLO miRNA Target Expression Vectorにクローニングし、Rn33B-A68B2M細胞に導入した。EHV-1非感染細胞と感染細胞のそれぞれに対しデュアルルシフェラーゼアッセイを行ったところ、EHV-1感染によりルシフェラーゼ活性の低下がみられたが、これはORF63の3'非翻訳領域をクローニングしていない空ベクターを導入した細胞でも同様にみとめられたため、pmirGLOベクター固有の配列を認識するmiRNAがEHV-1感染時に誘導される可能性が示唆された。また、空ベクターを導入した細胞とORF63の3'非翻訳領域をクローニングしたベクターを導入した細胞とを非感染状態で比較した場合、miRNAの作用を確認するホタルルシフェラーゼのみならず内部標準であるウミシイタケルシフェラーゼについても空ベクター導入細胞の方がより高い活性を示したことから、ORF63の3'非翻訳領域を認識し発現を負に制御する何らかの宿主因子の存在が推測された。また、BALB/cマウスにEHV-1を経鼻接種し、令和4年度の研究において同定されたEHV-1 IE 遺伝子のプロモーター領域より転写されるncRNAの発現をリアルタイムRT-PCRで検索したところ、感染後1日目の肺組織でIE遺伝子と共にncRNAの発現が認められた。
  日本学術振興会, 基盤研究(B), 北海道大学, 23K23773
• ウマヘルペスウイルス1型感染神経細胞におけるウイルス遺伝子発現制御機構の解明
  科学研究費助成事業
  2022年04月01日 - 2026年03月31日
  木村 享史; 青島 圭佑
  日本学術振興会, 基盤研究(B), 北海道大学, 22H02508
• 結核と鼻疽の制圧プロジェクト
  医療分野国際科学技術共同研究開発推進事業 地球規模課題対応国際科学技術協力プログラム
  2020年04月 - 2025年03月
  国立研究開発法人日本医療研究開発機構, 北海道大学、結核予防会結核研究所、モンゴル国立感染症センター、モンゴル生命科学大学獣医学研究所, 研究代表者
• レセプター遺伝子導入モデルを用いたウマヘルペスウイルス1型潜伏感染機構の解明
  科学研究費助成事業 基盤研究(B)
  2016年04月01日 - 2020年03月31日
  木村 享史; 青島 圭佑
  ウマヘルペスウイルス1型（EHV-1）は馬に呼吸器症状、流産および脊髄脳症を引き起す。EHV-1は神経細胞とリンパ球に潜伏感染することが報告されているが、その機序については不明な点が多く、これは小動物モデルおよびin vitroモデルが存在しないことによる。本研究では、EHV-1に感受性を有するin vitroモデルとマウスモデルをEHV-1エントリーレセプターの遺伝子導入によって作製、解析し、潜伏感染モデルとしての有用性を検証した。分化依存性にEHV-1感染に抵抗性を示すラット由来神経細胞株は、EHV-1の神経病原性と潜伏感染に関与する分子メカニズムの解明に有用であると考えられた。
  日本学術振興会, 基盤研究(B), 北海道大学, 16H05022
• ウシの黄色ブドウ球菌性乳房炎の慢性化におけるCXCL8の持続的放出の役割
  科学研究費助成事業 基盤研究(C)
  2015年04月01日 - 2018年03月31日
  渡部 淳; 木村 和弘; 木村 享史; 秦 英司; 中島 恵一; 林 智人
  黄色ブドウ球菌性乳房炎が慢性化する過程で観察されるケモカインCXCL8の持続的放出について、ウシ乳腺上皮細胞における CXCL8の発現は主に黄色ブドウ球菌リポテイコ酸等によって誘発され、ラクトフェリンのエラスターゼ分解産物である催炎性ラクトフェリン由来ペプチドもCXCL8発現に部分的に関与することが示唆された。また同乳房炎においてCXCL8同様に持続的に放出される好中球エラスターゼは好中球の細胞死に伴なって放出され、その細胞死には壊死や好中球細胞外トラップ形成が関わることが示唆された。
  日本学術振興会, 基盤研究(C), 国立研究開発法人農業・食品産業技術総合研究機構, 15K07731
• 神経細胞のフラビウイルス感受性を規定する宿主因子：細胞分化からのアプローチ
  科学研究費助成事業 挑戦的萌芽研究
  2014年04月01日 - 2016年03月31日
  木村 享史
  ラット中脳由来神経細胞株CSM14.1は分化依存的に日本脳炎ウイルス（JEV）感受性の低下を示す。分化状態によって発現が変動する遺伝子群をマイクロアレイ法にて解析し、これらのうちから神経細胞のウイルス感受性に関与する未知の宿主遺伝子を同定する目的で、未分化CSM14.1細胞での発現が分化CSM14.1に比較して高い遺伝子群より2個、分化CSM14.1細胞での発現が未分化CSM14.1細胞に比較して高い遺伝子群より2個の遺伝子を選別した。これら遺伝子を未分化CSM14.1細胞に過剰発現させ、JEV感受性の変動を解析した。
  日本学術振興会, 挑戦的萌芽研究, 北海道大学, 26660222
• レセプター遺伝子導入マウスを利用した抗ウマヘルペスウイルス1型戦略
  科学研究費補助金(基盤研究(B))
  2012年 - 2015年
  木村 享史
  ウマ主要組織適合遺伝子複合体（MHC）クラスⅠ分子はウマヘルペスウイルス1型（EHV-1）レセプターのエントリーレセプターとして機能する。全身諸臓器にウマMHCクラスⅠ遺伝子を発現するトランスジェニックマウス（Tgマウス）を作製し、EHV-1を経鼻感染させた。TgマウスではWTマウスと比較してより重度の肺炎を発症し、また、肺組織中により多数のウイルス感染細胞が認められた。以上の結果から、外来性に導入したウマMHCクラスIがマウスのEHV-1感受性の増強に関与することが示唆された。また、EHV-1の主要標的細胞であるT細胞に特異的にMHCクラスIを発現するTgマウスを作製した。
  文部科学省, 基盤研究(B), 北海道大学, 研究代表者, 競争的資金, 24380162
• ウシの黄色ブドウ球菌性乳房炎における好中球介在性炎症増幅機構の役割
  科学研究費助成事業 基盤研究(C)
  2010年 - 2012年
  渡部 淳; 秦 英司; 木村 和弘; 平井 綱雄; 木村 享史
  牛の黄色ブドウ球菌性乾乳期乳房炎における炎症が持続的に進行する特徴的病態に、連鎖的に乳汁中に放出されるインターロイキン-8(IL-8)(CXCL8ともいう)、好中球エラスターゼ、催炎性ラクトフェリン由来ペプチド(ラクトフェリンのエラスターゼによる分解産物)が関与することを明らかにした。また慢性乳房炎において、IL-8の分泌を抑制するトランスフォーミング成長因子-β2は炎症の鎮静化に関与することが示唆された。
  日本学術振興会, 基盤研究(C), 独立行政法人農業・食品産業技術総合研究機構, 22580347
• ウマヘルペスウイルス1型レセプターの機能解析とそれを基盤とした感染予防法の検討
  科学研究費補助金(基盤研究(B))
  2008年 - 2011年
  木村 享史; 澤 洋文
  ウマヘルペスウイルス1型(EHV-1)はアルファヘルペスウイルス亜科に属し、ウマに呼吸器症状、流産、脳脊髄炎を惹き起こす。臨床上特に問題となる流産と脳脊髄炎では、妊娠子宮、中枢神経系特異的に血管内皮細胞へのウイルス感染が生じ、それに続発する血管炎、血栓形成、循環障害が病態発生に大きな役割を果たしている。従って、血管内皮細胞へのウイルス感染は流産、脳脊髄炎の発症において最も重要なステップであるにも関わらず、その感受性を規定するウイルスレセプターに関しては不明な点が多い。本研究では、ウマ脳血管内皮細胞からクローニングしたEHV-1レセプターの機能解析を行い、レセプター遺伝子導入によるマウスモデルの作製とウイルスエンベロープ蛋白-レセプター相互作用を利用した感染予防法の検討を行う。
  文部科学省, 基盤研究(B), 北海道大学, 研究代表者, 競争的資金, 20380165
• フラビウイルス脳炎の新側面-ウイルス感染に起因する精神機能異常の病態解明-
  科学研究費補助金(挑戦的萌芽研究)
  2009年 - 2010年
  木村 享史
  日本脳炎ウイルス(JEV)感染ラットの脳内では低レベルのウイルスゲノムRNA複製が持続している。この感染状態に類似したin vitroシステムを確立する目的で、以下の実験を行った。ラット神経細胞由来株化細胞として、温度感受性SV40T抗原で不死化されたCSM14.1を使用した。JEVの構造蛋白遺伝子を組み込んだ発現プラスミドを作製し、ウエストナイルウイルス(WNV)非構造蛋白遺伝子とEGFP発現カセットを有するWNVレプリコン(ペンシルベニア大学より分与)と共に293T細胞へ導入することにより、上清中に産生されるVLPを回収した。CSM14.1細胞にVLPを感染させた場合、31℃にて維持した細胞では13.6%がGFP陽性を示した。一方、37℃下で72時間培養し神経系分化マーカーが発現した細胞では、VLPの感染により51%がGFP陽性を示し、37℃下での培養によってVLP感染率が低下することが明らかとなった。また、37℃にて培養した細胞では、31℃で維持した細胞と比較して、エンドサイトーシスによるJEV particleの取り込み効率に差異があることが示唆された。従って、レプリコンRNAの導入には31℃にて維持した細胞を使用することが適切であることが確認された。JEV感染ラットの脳内ではセロトニン産生酵素であるトリプトファン水解酵素(TPH)の遺伝子発現が上昇している。F344...
  文部科学省, 挑戦的萌芽研究, 北海道大学, 研究代表者, 競争的資金, 21658102
• 血液脳関門モデルを用いたウエストナイルウイルス神経侵襲メカニズムの解明
  科学研究費補助金(基盤研究(C))
  2006年 - 2007年
  木村 享史; 好井 健太朗; 澤 洋文
  1.ウエストナイルウイルス(WNV)が血液脳関門(Blood-brain barrier; BBB)を通過する機序には不明な点が多い。本研究では、ヒト臍静脈内皮細胞(HUVEC)をTranswell filterの上面に接着、単層培養を行い、BBBのin vitroモデルとして使用した。2.pCMVベクターにWNV NY99 6LP株およびEg101株の構造遺伝子(C、PrM、E)を組み込んだ発現プラスミドを作製した。これとWNVレプリコン(WNV非構造蛋白遺伝子全長と緑色蛍光蛋白EGFP発現カセットを有する)をBHK細胞に共導入し、ウイルス様粒子(Virus-like particles; VLPs)を作製した。3.WNV強毒株である 6LP株のVLPs(6LP-VLPs)および弱毒株であるg101株のVLPs(Eg-VLPs)をin vitro BBBモデルに感染させ、BBBを透過したVLPsの量を24時間後に測定した。Transwell内に接種した6LP-VLPsの約1/10量が下方のチャンバーから検出されたが、同様に接種したEg-VLPsは下方のチャンバーからほとんど検出されなかった。このように両者のin vitroBBB透過性には有意な差が認められ、ウイルスの毒力とBBB透過性との関連性が示唆された。次にHUVECに6LP-VLPsを感染させ、タイトジャンクション(...
  文部科学省, 基盤研究(C), 北海道大学, 研究代表者, 競争的資金, 18580302
• 野生のニホンジカは人あるいは他の動物種の感染源になり得るか?
  科学研究費補助金(基盤研究(B))
  2004年 - 2006年
  鈴木 正嗣; 梶 光一; 山内 貴義; 有川 二郎; 横山 真弓; 堀内 基広; 木村 享史
  1.ニホンジカ(976頭)とニホンイノシシ(87頭)から得た血清を用い,ELISA法とウエスタンブロット法によりE型肝炎に対する血清学的診断を行った.その結果,それぞれの種で2.6%および2.3%が抗体陽性と判断された.イノシシにおいては,RT-PCR法により3頭でHEV-RNAが確認されたが,捕獲状況からこれらは同腹子と考えられた2.野生のニホンイノシシ(88頭)から得た血清を用い,ELISA法と顕微鏡下凝集試験(MAT)により,レプトスピフに対する抗体の検出を行った.その結果,12検体(13.6%)が抗体陽性と判断され,さらにMATでは血清型copenhageni, australis, bratislavaの抗体が検出された.そのため,捕獲ならびに解体にともなう人や猟犬に対する感染リスクが示唆された.3.野生のニホンジカ173頭を材料に,糞便培養法,LAMP法,nested PCR法によりヨーネ菌の検出を試みた.その結果,糞便培養法では菌は確認されなかった.また,LAMP法とnested PCR法でもヨーネ菌DNAは検出されなかった.4.北海道産の野生ニホンジカ(エゾシカ)においては,末梢血よりRickettsia helveticaとEhrlichiamurisの遺伝子が確認された.5.岩手県で捕獲された野生ニホンジカからは,槍形吸虫Dicrocoelium chin...
  文部科学省, 基盤研究(B), 北海道大学->岐阜大学, 連携研究者, 競争的資金, 16380202
• マウス脳継代により獲得されたウマヘルペスウイルス1型神経病原性の分子基盤
  科学研究費補助金(若手研究(B))
  2002年 - 2003年
  木村 享史
  ウマヘルペスウイルス1型(EHV-1)の神経向性は他のヘルペスウイルスに比較して非常に弱いことが知られているが、脳継代によって作出したEHV-1神経馴化株(NHH1)は親株(HH1)に比べて強い神経病原性を示す。脳継代による変異領域を同定する目的で、両ウイルス株のDNAを比較解析した。LA-PCR法によって13Kbに至るウイルスDNA断片を複数増幅し、RFLP解析を行ったが、両ウイルス間に差異は検出されなかった。平成14年度の解析により、NHH1はHH1に比べてより広範囲な組織向性を示すことが明らかとなっているため、細胞への吸着、侵入に関与するエンベロープ蛋白に変異が生じている可能性が考えられた。そこで、NHH1、HH1のgB遺伝子、gD遺伝子をそれぞれシークエンスしたが、両ウイルス株間でコードされるアミノ酸配列に相違は認められなかった。平成14年度に行った解析により、NHH1、HH1の示す神経侵襲性の差異が脳血管内皮細胞への感染性によって一部規定される可能性が考えられた。また、馬のEHV-1脳脊髄炎においても血行性にCNSに到達したウイルスが脳血管内皮細胞に感染することが知られている。そこで、馬、マウスの大脳皮質より脳微小血管内皮細胞(BMEC)を分離、培養し、HH1株に対する感受性を検討した。その結果、馬BMECはEHV-1感受性であり、エンドサイトーシスによってウイルス...
  文部科学省, 若手研究(B), 北海道大学, 研究代表者, 競争的資金, 14760197
• アルファウイルス脳炎の病態を制御する細胞性免疫因子の解明
  科学研究費補助金(特定領域研究(C))
  2001年 - 2001年
  木村 享史
  神経強毒性シンドビスウイルス(NSV)は成マウスに致死性(死亡率70〜100%)の急性ウイルス性脳炎を引き起こすが、耐過マウスには海馬組織欠損を特徴とする水頭症様病変が頻繁に認められる。本研究はこの海馬組織傷害に関与する細胞性免疫因子の同定を目的として行われた。C57BL/6マウス(B6)および同系のCD4遺伝子欠損マウス(CD4 -/-)、CD8α遺伝子欠損マウス(CD8 -/-)、recombination activating gene 1遺伝子欠損マウス(RAG -/-)にNSVを脳内接種し、接種後24時間目に抗NSV免疫血清を腹腔内投与することによってマウスを人為的に耐過させた。B6マウスにはマクロファージ、リンパ球浸潤を伴った海馬組織欠損が認められ、同病変は脳内から感染性ウイルスが消失した後に形成された。CD4 -/-マウスの海馬組織欠損は軽度であったが、CD8 -/-マウスはB6マウスと同様の水頭症病変を形成した。一部のRAG -/-マウスにおいてもマクロファージ浸潤を伴った重度の水頭症病変が形成された。TUNEL法陽性海馬分子層ニューロン数は海馬組織中に浸潤するCD4陽性細胞数およびマクロファージ数と比例したが、CD8陽性細胞数との相関は認められなかった。なお、抗CD4および抗CD8モノクローナル抗体投与によって作成したCD4陽性細胞欠損マウス、CD8陽性細胞...
  文部科学省, 特定領域研究(C), 北海道大学, 研究代表者, 競争的資金, 13226002
• インターロイキン-2遺伝子導入マウスにおける小脳病変の形成機序に関する実験的研究
  科学研究費補助金(奨励研究(A))
  1996年 - 1996年
  木村 享史
  ヒトIL-2 (hIL-2)ゲノムDNAを導入して作製したトランスジェニックマウス(hIL-2マウス)を免疫組織化学的、分子生物学的に解析し、以下の知見を得た。1.hIL-2マウスの小脳病変の免疫組織化学的検索5週齢のhIL-2マウスの小脳凍結切片を抗Thy-1抗体を用いた酵素抗体法によって検索したところ、クモ膜下腔に集簇するリンパ球のうち多くのものはThy-1陽性を呈した。2.hIL-2発現細胞の同定9日齢のhIL-2マウスの小脳パラフィン包埋切片に対し、hIL-2遺伝子を特異的に増幅するプライマー対を用いたRT-in situPCR法を施行した。hIL-2mRNAの5'末端を増幅するプライマー対と、第2エクソンから第3エクソンにわたる領域を増幅するプライマー対の2種類を用いて解析を行った結果、いずれのプライマー対を用いた場合においても、プルキンエ細胞層に限局して弱いシグナルが観察された。クモ膜下腔に浸潤している少数の炎症性細胞にシグナルは認められなかった。3.小脳において発現しているhIL-2mRNAの解析hIL-2マウス小脳mRNAからRT-PCR法によって第1イントロンを含んだhIL-2primary transcriptを増幅した。増幅したcDNA (293bp)をpGEM-4Zベクターにクローニングし、ジデオキシ法による塩基配列の解読を行った。その結果、第1イント...
  文部科学省, 奨励研究(A), 北海道大学, 研究代表者, 競争的資金, 08760266
• 神経細胞の細胞骨格ニューロフィラメントの生物学的並びに病理学的意義の究明
  科学研究費補助金(一般研究(B), 基盤研究(B))
  1995年 - 1996年
  板倉 智敏; 木村 亨史; 落合 謙爾
  1.ニューロフィラメント(NF)欠損ウズラ(Quv)の本態についてQuvの末梢神経線維における軸索と髄鞘の変化,およびその相関関係を調べた.無髄神経線維では,NF欠損を代償してマイクロチューブ(MT)数が増加しているようであった.有髄神経線維では,軸索の大きさが髄鞘層数の規定因子ではないと判断された.次に,NFの神経線維再生への関与を調べた.このため,Quv坐骨神経を鉗子で押して砕き,2週間後にこれより末梢部位を形態学的に調べた.この結果,Quvでは正常対照例より再生神経線維が少なく,NF欠損はその再生を遅延させることが明らかとなった.さらに,NFの欠損が三量体型GTP結合(G)蛋白質に影響を及ぼすか否かを検討した.G蛋白質はQuvでは正常ウズラよりも増量していたが,これがQuvの振戦症状発現に関与しているか否かは明らかではない.2.NF欠損ウズラ(Quv)に対する神経毒の影響Quvに対して,神経毒であるアクリルアミドに続いてtri-ortho-cresyl-phosphate(TOCP)の影響を調べた.TOCPの連続投与は,正常ウズラの脊髄白質の神経路に遠位軸索症を引き起こしたが,Quvにはその変化は生じなかった.よってNFの存在がその病変発現に関与していることは明らかであった.一方,TOCPの正常およびQuvウズラへの投与は,軸索終末変性を両者に引き起こし,この変性病変発...
  文部科学省, 一般研究(B), 基盤研究(B), 北海道大学, 競争的資金, 07456127
• インターロイキン-2遺伝子導入マウスにおける神経病変の発症機構に関する実験的研究
  科学研究費補助金(奨励研究(A))
  1995年 - 1995年
  木村 享史
  ヒトIL-2ゲノムDNAを導入して作製したトランスジェニックマウス(hIL-2マウス)を解析し、以下の知見を得た。1.hIL-2マウスの組織学的検索9日令、5週令および12週令の雄マウスについて病理組織学的検索を行ったところ、小脳、皮膚に限局して病変が認められた。9日令の小脳では、クモ膜下腔にリンパ球、マクロファージ、好中球の集簇が認められた。5週令、12週令ではクモ膜下腔のリンパ球浸潤に加え脂肪顆粒細胞が小脳実質内に浸潤し、これに伴って小脳皮質の菲薄化、小脳小葉の縮小が認められた。9日令の皮膚には変化が認められなかったが、5週令、12週令の皮膚では、真皮における毛包および血管を中心としたリンパ球、マクロファージ浸潤ならびに毛包、皮脂腺の消失が生じていた(第120回日本獣医学会発表、1995年11月)。2.hIL-2発現組織の同定9日令、5週令、12週令のhIL-2マウスの前進諸臓器ならびに末梢血白血球からtotal RNAを抽出し、ヒトhIL-2を特異的に増幅するプライマーペアを用いてRT-PCRを行ったところ、9日令、5週令の小脳、皮膚12週令の皮膚、体表リンパ節に特異的に導入遺伝子の発現が確認された(第120回日本獣医学会発表、1995年11月)。3.抗神経組織抗体の存在の有無の検討C57BL/6マウス小脳ホモジネートをhIL-2マウス血清を抗体として用いたImmuno...
  文部科学省, 奨励研究(A), 北海道大学, 研究代表者, 競争的資金, 07760289