研究者業績

高橋 雅春

タカハシ マサハル  (Masaharu Takahashi)

基本情報

所属
自治医科大学 医学部感染・免疫学講座ウイルス学部門 講師
学位
農学修士(岩手大学)
博士(医学)(自治医科大学(JMU))

J-GLOBAL ID
200901084896818128
researchmap会員ID
1000300021

研究キーワード

 2

論文

 211
  • Shigeo Nagashima, Putu Prathiwi Primadharsini, Masaharu Takahashi, Takashi Nishiyama, Kazumoto Murata, Hiroaki Okamoto
    Pathogens 13(12) 1130-1130 2024年12月20日  
    Hepatitis E virus (HEV) exists in two distinct forms: a non-enveloped form (neHEV), which is present in feces and bile, and a quasi-enveloped form (eHEV), found in circulating blood and culture supernatants. This study aimed to elucidate the roles of Ras-associated binding 13 (Rab13) and protein kinase A (PKA) in the entry mechanisms of both eHEV and neHEV, utilizing small interfering RNA (siRNA) and chemical inhibitors. The results demonstrated that the entry of both viral forms is dependent on Rab13 and PKA. Further investigation into the involvement of tight junction (TJ) proteins revealed that the targeted knockdown of zonula occludens-1 (ZO-1) significantly impaired the entry of both eHEV and neHEV. In addition, in ZO-1 knockout (KO) cells inoculated with either viral form, HEV RNA levels in culture supernatants did not increase, even up to 16 days post-inoculation. Notably, the absence of ZO-1 did not affect the adsorption efficiency of eHEV or neHEV, nor did it influence HEV RNA replication. In cell-to-cell spread assays, ZO-1 KO cells inoculated with eHEV showed a lack of expression of HEV ORF2 and ORF3 proteins. In contrast, neHEV-infected ZO-1 KO cells showed markedly reduced ORF2 and ORF3 protein expression within virus-infected foci, compared to non-targeting knockout (NC KO) cells. These findings underscore the crucial role of ZO-1 in facilitating eHEV entry and mediating the cell-to-cell spread of neHEV in infected cells.
  • Tominari Kobayashi, Masaharu Takahashi, Satoshi Ohta, Yu Hoshino, Kentaro Yamada, Suljid Jirintai, Putu Prathiwi Primadharsini, Shigeo Nagashima, Kazumoto Murata, Hiroaki Okamoto
    Viruses 16(9) 1400-1400 2024年8月31日  
    The zoonotic transmission of hepatitis E virus (HEV) genotypes 3 (HEV-3) and 4 (HEV-4), and rabbit HEV (HEV-3ra) has been documented. Vaccination against HEV infection depends on the capsid (open reading frame 2, ORF2) protein, which is highly immunogenic and elicits effective virus-neutralizing antibodies. Escherichia coli (E. coli) is utilized as an effective system for producing HEV-like particles (VLPs). However, research on the production of ORF2 proteins from these HEV genotypes in E. coli to form VLPs has been modest. In this study, we constructed 21 recombinant plasmids expressing various N-terminally and C-terminally truncated HEV ORF2 proteins for HEV-3, HEV-3ra, and HEV-4 in E. coli. We successfully obtained nine HEV-3, two HEV-3ra, and ten HEV-4 ORF2 proteins, which were primarily localized in inclusion bodies. These proteins were solubilized in 4 M urea, filtered, and subjected to gel filtration. Results revealed that six HEV-3, one HEV-3ra, and two HEV-4 truncated proteins could assemble into VLPs. The purified VLPs displayed molecular weights ranging from 27.1 to 63.4 kDa and demonstrated high purity (74.7–95.3%), as assessed by bioanalyzer, with yields of 13.9–89.6 mg per 100 mL of TB medium. Immunoelectron microscopy confirmed the origin of these VLPs from HEV ORF2. Antigenicity testing indicated that these VLPs possess characteristic HEV antigenicity. Evaluation of immunogenicity in Balb/cAJcl mice revealed robust anti-HEV IgG responses, highlighting the potential of these VLPs as immunogens. These findings suggest that the generated HEV VLPs of different genotypes could serve as valuable tools for HEV research and vaccine development.
  • Tatsuo Kanda, Tian-Cheng Li, Masaharu Takahashi, Shigeo Nagashima, Putu Prathiwi Primadharsini, Satoshi Kunita, Reina Sasaki-Tanaka, Jun Inoue, Atsunori Tsuchiya, Shingo Nakamoto, Ryuzo Abe, Keiichi Fujiwara, Osamu Yokosuka, Ryosuke Suzuki, Koji Ishii, Hiroshi Yotsuyanagi, Hiroaki Okamoto
    Hepatology research : the official journal of the Japan Society of Hepatology 2024年6月14日  
    Acute hepatitis E was considered rare until reports emerged affirming the existence of hepatitis E virus (HEV) genotypes 3 and 4 infections in Japan in the early 2000s. Extensive studies by Japanese researchers have highlighted the pivotal role of pigs and wild animals, such as wild boars and deer, as reservoirs for HEV, linking them to zoonotic infections in Japan. Currently, when hepatitis occurs subsequent to the consumption of undercooked or grilled pork, wild boar meat, or offal (including pig liver and intestines), HEV infection should be considered. Following the approval of anti-HEV immunoglobulin A antibody as a diagnostic tool for hepatitis E by Japan's Health Insurance System in 2011, the annual number of diagnosed cases of HEV infection has surged. Notably, the occurrence of post-transfusion hepatitis E promoted nationwide screening of blood products for HEV using nucleic acid amplification tests since 2020. Furthermore, chronic hepatitis E has been observed in immunosuppressed individuals. Considering the significance of hepatitis E, heightened preventive measures are essential. The Japan Agency for Medical Research and Development Hepatitis A and E viruses (HAV and HEV) Study Group, which includes special virologists and hepatologists, held a virtual meeting on February 17, 2024. Discussions encompassed pathogenesis, transmission routes, diagnosis, complications, severity factors, and ongoing and prospective vaccination or treatments for hepatitis E. Rigorous assessment of referenced studies culminated in the formulation of recommendations, which are detailed within this review. This comprehensive review presents recent advancements in HEV research and Japanese clinical practice guidelines for HEV infection.
  • Putu Prathiwi Primadharsini, Masaharu Takahashi, Tsutomu Nishizawa, Yukihiro Sato, Shigeo Nagashima, Kazumoto Murata, Hiroaki Okamoto
    Viruses 16(6) 842-842 2024年5月24日  
    Hepatitis E virus (HEV) can cause self-limiting acute and chronic hepatitis infections, particularly in immunocompromised individuals. In developing countries, HEV is mainly transmitted via drinking contaminated water, whereas zoonotic transmission dominates the route of infection in developed countries, including Japan. Pigs are an important reservoir for HEV infection. Wild boars, which share the same genus and species as domestic pigs, are also an HEV reservoir. During our nationwide study of HEV infection in wild boar populations in Japan, a genotype 6 (HEV-6) strain, wbJHG_23, was isolated in Hyogo Prefecture in 2023. The genomic length was 7244 nucleotides, excluding the poly(A) tract. The wbJHG_23 strain exhibited the highest nucleotide identity throughout its genome with two previously reported HEV-6 strains (80.3–80.9%). Conversely, it displayed lower similarity (73.3–78.1%) with the HEV-1–5, HEV-7, and HEV-8 strains, indicating that, although closely related, the wbJHG_23 strain differs significantly from the reported HEV-6 strains and might represent a novel subtype. The wbJHG_23 strain successfully infected the human-derived cancer cell lines, PLC/PRF/5 and A549 1-1H8 cells, suggesting that HEV-6 has the potential for zoonotic infection. An infectious cDNA clone was constructed using a reverse genetics system, and a cell culture system supporting the efficient propagation of the HEV-6 strain was established, providing important tools for further studies on this genotype. Using this cell culture system, we evaluated the sensitivity of the wbJHG_23 strain to ribavirin treatment. Its good response to this treatment suggested that it could be used to treat human infections caused by HEV-6.
  • Shigeo Nagashima, Putu Prathiwi Primadharsini, Takashi Nishiyama, Masaharu Takahashi, Kazumoto Murata, Hiroaki Okamoto
    JOURNAL OF VIROLOGY 2023年9月  
  • Masaharu Takahashi, Satoshi Kunita, Tsutomu Nishizawa, Hiroshi Ohnishi, Putu Prathiwi Primadharsini, Shigeo Nagashima, Kazumoto Murata, Hiroaki Okamoto
    VIRUSES-BASEL 15(7) 2023年7月  
  • Putu Prathiwi Primadharsini, Shigeo Nagashima, Toshinori Tanaka, Suljid Jirintai, Masaharu Takahashi, Kazumoto Murata, Hiroaki Okamoto
    VIRUSES-BASEL 15(4) 2023年4月  
  • Satoshi Takakusagi, Hitoshi Takagi, Yuichi Yamazaki, Takashi Kosone, Shigeo Nagashima, Masaharu Takahashi, Kazumoto Murata, Hiroaki Okamoto
    Clinical journal of gastroenterology 16(2) 206-215 2023年4月  
    A woman in her late 70 s was diagnosed with liver injury at a health examination. Despite treatment with ursodeoxycholic acid at a nearby hospital, her transaminase levels elevated in two peaks. She was transferred to our hospital 77 days after the health examination. She weighed 42 kg and had a low body mass index of 19.8 kg/m2. Viral markers, including immunoglobulin A (IgA) against hepatitis E virus (anti-HEV IgA), were negative. Drug-induced liver injury was negligible. We suspected autoimmune hepatitis because of the patient's female gender and positive antinuclear antibody. However, prednisolone and azathioprine failed to completely improve her hepatitis. On day 643, anti-HEV IgA was re-evaluated and found to be positive. She was diagnosed with autochthonous chronic hepatitis E because the virus strains in the preserved serum on day 77 and the serum on day 643 had identical nucleotide sequences (genotype 3a). Following prednisolone and azathioprine discontinuation, ribavirin (RBV) was administered for 3 months. HEV RNA disappeared and remained negative for more than 6 months after the cessation of RBV. The HEV RNA titer of 6.2 log10 copies/mL on day 77 was unusually high 2.5 months after the onset, suggesting that hepatitis E had already been chronic before immunosuppressive treatment for possible autoimmune hepatitis. After getting married at 23 years old, she had been a housewife and had no comorbidities that might deteriorate her immunity. Chronicity should be kept in mind when encountering HEV infection in elderly and underweight patients.
  • Putu Prathiwi Primadharsini, Shigeo Nagashima, Masaharu Takahashi, Kazumoto Murata, Hiroaki Okamoto
    VIRUSES-BASEL 14(11) 2022年11月  
  • Tsutomu Nishizawa, Masaharu Takahashi, Hiroyuki Matsuoka, Akira Nishizono, Seigo Yamamoto, Emiko Fukui, Hitoshi Mizuo, Manri Kawakami, Kazumoto Murata, Hiroaki Okamoto
    Virus Research 314 198749-198749 2022年6月  
  • Masaharu Takahashi, Satoshi Kunita, Manri Kawakami, Teruki Kadosaka, Hiromi Fujita, Nobuhiro Takada, Masao Miyake, Tominari Kobayashi, Hiroshi Ohnishi, Shigeo Nagashima, Kazumoto Murata, Hiroaki Okamoto
    VIRUS RESEARCH 314 2022年6月  
  • Izumi Hasegawa, Tatsunori Nakano, Hiroki Koguchi, Naruomi Jinno, Noboru Hirashima, Shigeo Nagashima, Masaharu Takahashi, Kazumoto Murata, Hiroaki Okamoto
    Clinical journal of gastroenterology 2022年5月4日  
    A case of subclinical hepatitis E virus (HEV) infection was detected by nucleic acid amplification test on blood donation. The patient was followed-up until day 220 after the blood donation but showed no symptoms throughout the observation period. Aspartate aminotransferase and alanine aminotransferase levels reached the maximum values on day 37 with a slight increase but remained in normal ranges from day 67 to 220. The quantity of HEV RNA at the initial examination on day 13 was 1.1 × 102 copies/mL, which increased to 2.8 × 103 copies/mL by day 37. It was not detected from day 67 to 220. Immunoglobulin G class antibody to HEV (anti-HEV IgG) was below the cut-off value until day 37 and exceeded the cut-off value to positive on day 67, accompanied by normalization of liver function and negative conversion of HEV RNA. Thereafter, the titer decreased gradually, falling below the cut-off value on day 163, and continuing negative until day 220. Although the persistent duration of anti-HEV IgG positive is believed to be generally long, it was within only 126 days for this subclinical case. Further investigation is needed to determine whether short-term positivity for anti-HEV IgG is typical in subclinical HEV infection.
  • Putu Prathiwi Primadharsini, Shigeo Nagashima, Takashi Nishiyama, Masaharu Takahashi, Kazumoto Murata, Hiroaki Okamoto
    Journal of Virology 96(6) 2022年2月2日  
  • Masaharu Takahashi, Akira Nishizono, Manri Kawakami, Emiko Fukui, Emiko Isogai, Hiroyuki Matsuoka, Seigo Yamamoto, Hitoshi Mizuo, Shigeo Nagashima, Kazumoto Murata, Hiroaki Okamoto
    Virus research 308 198645-198645 2022年1月15日  
    Hepatitis E virus (HEV) is a zoonotic agent mainly transmitted through the consumption of uncooked or undercooked meat products derived from infected animals. In Japan, domestic pigs and wild boars are the major animal reservoirs, and whether or not deer are an HEV reservoir remains controversial. We analyzed 395 serum and 199 liver samples from 405 sika deer (Cervus nippon) caught in the wild between 1997 and 2020 in 11 prefectures of Japan for markers of HEV infection. Overall, 17 deer had anti-HEV IgG (4.3%), while 1 (0.2%) had HEV RNA (genotype 3b), indicating the occurrence of ongoing HEV infection in wild deer in Japan. An analysis of the complete HEV genome (deJOI_14) recovered from a viremic deer in Oita Prefecture revealed only 88.8% identity with the first HEV strain in sika deer (JDEER-Hyo03L) in Japan, being closest (96.3%) to the HEV obtained from a hepatitis patient living in the same prefecture. Of note, the deJOI_14 strain was 8.7-9.0% different from the wild boar HEV strains obtained in the same habitat and the same year, suggesting that difference in infected HEV strains between boar and deer may be explained by the limited possibility of close contact with each other, although boars are a known source of HEV infection. Increased numbers of hepatitis E cases after consumption of raw or undercooked meat products of wild deer have been reported in Japan. These results suggest a low but nonnegligible zoonotic risk of HEV infection in wild deer in this country.
  • 中野 達徳, 西垣 洋一, 林 秀樹, 田尻下 聡子, 岩佐 太誠, 冨田 栄一, 鈴木 祐介, 清水 省吾, 杉原 潤一, 長嶋 茂雄, 高橋 雅春, 岡本 宏明, 村田 一素
    肝臓 63(1) 35-38 2022年1月  
  • Takashi Nishiyama, Koji Umezawa, Kentaro Yamada, Masaharu Takahashi, Satoshi Kunita, Mulyanto, Isao Kii, Hiroaki Okamoto
    Pathogens 11(1) 24-24 2021年12月26日  
    The hepatitis E virus (HEV) is a causative agent of hepatitis E. HEV virions in circulating blood and culture media are quasi-enveloped, while those in feces are nonenveloped. The capsid (ORF2) protein associated with an enveloped HEV virion is reported to comprise the translation product of leucine 14/methionine 16 to 660 (C-terminal end). However, the nature of the ORF2 protein associated with fecal HEV remains unclear. In the present study, we compared the molecular size of the ORF2 protein among fecal HEV, cell-culture-generated HEV (HEVcc), and detergent-treated protease-digested HEVcc. The ORF2 proteins associated with fecal HEV were C-terminally truncated and showed the same size as those of the detergent-treated protease-digested HEVcc virions (60 kDa), in contrast to those of the HEVcc (68 kDa). The structure prediction of the ORF2 protein (in line with previous studies) demonstrated that the C-terminal region (54 amino acids) of an ORF2 protein is in flux, suggesting that proteases target this region. The nonenveloped nondigested HEV structure prediction indicates that the C-terminal region of the ORF2 protein moves to the surface of the virion and is unnecessary for HEV infection. Our findings clarify the maturation of nonenveloped HEV and will be useful for studies on the HEV lifecycle.
  • Tominari Kobayashi, Masaharu Takahashi, Satoshi Ohta, Shigeo Nagashima, Putu Prathiwi Primadharsini, Mulyanto, Satoshi Kunita, Kazumoto Murata, Hiroaki Okamoto
    Virus research 302 198483-198483 2021年9月  
    Rat hepatitis E virus (HEV) has been isolated from wild rats worldwide and the potential of zoonotic transmission has been documented. Escherichia coli (E. coli) is utilized as an effective system for producing HEV-like particles. However, the production of rat HEV ORF2 proteins in E. coli forming virus-like particles (VLPs) has not yet been reported. In this study, nine rat HEV ORF2 proteins of the ratELOMB-131L strain with truncated N- and C-termini (amino acids 339-594, 349-594, 351-594, 354-594, 357-594, 357-599, 357-604, 357-609, and 357-614 of ORF2 protein) were expressed in E. coli and the 357-614 protein self-assembled most efficiently. A bioanalyzer showed that the purified 357-614 protein has a molecular weight of 33.5 kDa and a purity of 93.2%. Electron microscopy revealed that the purified 33.5 kDa protein formed VLPs with a diameter of 21-52 (average 32) nm, and immunoelectron microscopy using an anti-rat HEV ORF2 monoclonal antibody (TA7014) indicated that the observed VLPs were derived from rat HEV ORF2. The VLPs attached to and entered the PLC/PRF/5 cells and blocked the neutralization of rat HEV by TA7014, suggesting that the VLPs possess the antigenic structure of infectious rat HEV particles. In addition, rat HEV VLPs showed high immunogenicity in mice. The present results would be useful for future studies on the development of VLP-based vaccines for HEV prevention in a rat model and for the prevention of rat HEV infection in humans.
  • Satoshi Takakusagi, Hitoshi Takagi, Yozo Yokoyama, Kazuko Kizawa, Kyoko Marubashi, Takashi Kosone, Shigeo Nagashima, Masaharu Takahashi, Kazumoto Murata, Hiroaki Okamoto
    CLINICAL JOURNAL OF GASTROENTEROLOGY 14(4) 1202-1210 2021年8月  
  • Tsutomu Nishizawa, Masaharu Takahashi, Bira Tsatsralt-Od, Khurelbaatar Nyamdavaa, Nyamkhuu Dulmaa, Byankhuu Osorjin, Erdene-Ochir Tseren-Ochir, Tumenjargal Sharav, Chimedtseren Bayasgalan, Boldbaatar Sukhbaatar, Shigeo Nagashima, Kazumoto Murata, Hiroaki Okamoto
    VIRUS RESEARCH 299 2021年7月  
  • 浦和 尚史, 吉澤 尚彦, 小島 裕治, 橋本 章, 清水 敦哉, 田中 隆光, 濱岡 志麻, 小林 壮一朗, 中野 達徳, 岡野 宏, 長嶋 茂雄, 高橋 雅春, 岡本 宏明, 村田 一素
    肝臓 62(6) 384-386 2021年6月  
  • Yukio Oshiro, Hiroshi Harada, Kiyoshi Hasegawa, Naotake Akutsu, Tomoharu Yoshizumi, Naoki Kawagishi, Koji Nanmoku, Naotsugu Ichimaru, Kenichi Okamura, Masahiro Ohira, Yoshihiro Itabashi, Nobuhiro Fujiyama, Kentaro Ide, Hideaki Okajima, Kohei Ogawa, Kosei Takagi, Hidetoshi Eguchi, Masahiro Shinoda, Kiyotaka Nishida, Jiro Shimazaki, Mitsugi Shimoda, Masaharu Takahashi, Hiroaki Okamoto, Shuji Suzuki
    Hepatology research : the official journal of the Japan Society of Hepatology 51(5) 538-547 2021年5月  
    AIM: Studies regarding changes in antibodies to hepatitis E virus (HEV) after HEV infection in organ transplant patients are limited. This study aimed to clarify HEV infection trends in organ transplant patients who contracted HEV using data from a previous Japanese nationwide survey. METHODS: This study was undertaken from 2012 to 2019. Among 4518 liver, heart, and kidney transplant patients, anti-HEV immunoglobulin G (IgG) antibodies were positive in 164; data were collected from 106 of these patients, who consented to participate in the study. In total, 32 liver transplant patients, seven heart transplant patients, and 67 kidney transplant patients from 16 institutions in Japan were examined for IgG, IgM, and IgM antibodies to HEV and the presence of HEV RNA in the serum. The χ2 -test was used to determine the relationship between the early and late postinfection groups in patients with anti-HEV IgG positive-to-negative conversion rates. The Mann-Whitney U-test was used to compare clinical factors. RESULTS: Anti-HEV IgG positive-to-negative conversion occurred in 25 (23.6%) of 106 organ transplant patients. Of eight patients with hepatitis E who tested positive for HEV RNA, one (14.0%) had anti-HEV IgG positive-to-negative conversion. Twenty-four (24.5%) of 98 patients negative for HEV RNA had anti-HEV IgG positive-to-negative conversion. CONCLUSIONS: This study revealed, for the first time, the changes in HEV antibodies in organ transplant patients. Loss of anti-HEV IgG could often occur unexpectedly in organ transplant patients with previous HEV infection.
  • Wenjing Zhang, Yasushi Ami, Yuriko Suzaki, Yen Hai Doan, Suljid Jirintai, Masaharu Takahashi, Hiroaki Okamoto, Naokazu Takeda, Masamichi Muramatsu, Tian-Cheng Li
    Transboundary and emerging diseases 68(2) 615-625 2021年3月  
    Rabbit hepatitis E virus (HEV) is a novel zoonotic infectious agent. Although a cell culture system to grow the virus has been established, there is currently no reverse genetics system for generating the virus. In this study, capped genomic rabbit HEV RNAs generated by in vitro transcription were transfected into PLC/PRF/5 cells, and the recovered viruses were subsequently passaged in the cells. The cell culture supernatant was capable of infecting rabbits negative for anti-HEV antibody by intravenous and oral inoculation, indicating that rabbit HEV generated by the reverse genetics system is infectious. Genome-wide analyses indicated that no nucleotide sequence change occurred in the virus genomes that were recovered from the cell culture supernatant after transfection and passaged one time or in the virus genomes recovered from faecal specimens of the infected rabbits. Ribavirin, a broad-spectrum anti-viral inhibitor, efficiently abrogated virus replication ex vivo and transiently suppressed the virus growth in the virus-infected rabbits, suggesting that this reagent is a candidate for therapeutic treatment. In addition, transmission of rabbit HEV to rabbits caused persistent infection, suggesting that the virus-infected rabbit could be an animal model for virus-induced hepatitis. The infectious rabbit HEV produced by a reverse genetics system would be useful to elucidate the mechanisms of HEV replication and the pathogenesis of viral hepatitis.
  • Naoto Sato, Shunji Watanabe, Kouichi Miura, Naoki Morimoto, Yoshinari Takaoka, Hiroaki Nomoto, Norio Isoda, Shigeo Nagashima, Masaharu Takahashi, Hiroaki Okamoto, Hironori Yamamoto
    JOURNAL OF MEDICAL VIROLOGY 92(12) 3572-3583 2020年12月  
  • Masaharu Takahashi, Tsutomu Nishizawa, Yukihiro Sato, Shinichi Miyazaki, Tatsuya Aikawa, Kozo Ashida, Tomoko Tamaru, Kunihiko Oguro, Fumihiro Hayakawa, Hiroyuki Matsuoka, Hideaki Ozaki, Yuuji Kodera, Masahiko Irokawa, Hideo Hirose, Shigeo Nagashima, Manri Kawakami, Hitoshi Mizuo, Hiroaki Okamoto, Kazumoto Murata
    Virus Research 287 198106-198106 2020年10月  
  • 山崎 勇一, 植原 大介, 金山 雄樹, 須賀 孝慶, 上野 敬史, 畑中 健, 高草木 智史, 戸島 洋貴, 滝澤 大地, 長沼 篤, 小曽根 隆, 中島 弘明, 佐藤 賢, 柿崎 暁, 高木 均, 浦岡 俊夫, 高橋 雅春, 長嶋 茂雄, 岡本 宏明
    肝臓 61(9) 478-481 2020年9月  
  • 中川 直樹, 中野 達徳, 阪口 亮平, 福井 淑崇, 樋口 国博, 中島 滋人, 高司 智史, 三好 美穂, 長嶋 茂雄, 高橋 雅春, 渡邉 省三, 竹井 謙之, 岡本 宏明
    肝臓 61(5) 270-272 2020年5月  
  • Hiroshi Okano, Tatsunori Nakano, Ryugo Ito, Ami Tanaka, Yuji Hoshi, Keiji Matsubayashi, Hiroki Asakawa, Kenji Nose, Satomi Tsuruga, Tomomasa Tochio, Hiroaki Kumazawa, Yoshiaki Isono, Hiroki Tanaka, Shimpei Matsusaki, Tomohiro Sase, Tomonori Saito, Katsumi Mukai, Akira Nishimura, Keiki Kawakami, Shigeo Nagashima, Masaharu Takahashi, Hiroaki Okamoto
    Clinical Journal of Gastroenterology 13(2) 252-259 2020年4月  
  • Putu Prathiwi Primadharsini, Shigeo Nagashima, Masaharu Takahashi, Tominari Kobayashi, Takashi Nishiyama, Tsutomu Nishizawa, Jiro Yasuda, Mulyanto, Hiroaki Okamoto
    Virus research 278 197868-197868 2020年3月  査読有り
    Recent reports have shown that rat hepatitis E virus (HEV) is capable of infecting humans. We also successfully propagated rat HEV into human PLC/PRF/5 cells, raising the possibility of a similar mechanism shared by human HEV and rat HEV. Rat HEV has the proline-rich sequence, PxYPMP, in the open reading frame 3 (ORF3) protein that is indispensable for its release. However, the release mechanism remains unclear. The overexpression of dominant-negative (DN) mutant of vacuolar protein sorting (Vps)4A or Vps4B decreased rat HEV release to 23.9 % and 18.0 %, respectively. The release of rat HEV was decreased to 8.3 % in tumor susceptibility gene 101 (Tsg101)-depleted cells and to 31.5 % in apoptosis-linked gene 2-interacting protein X (Alix)-depleted cells. Although rat HEV ORF3 protein did not bind to Tsg101, we found a 90-kDa protein capable of binding to wild-type rat HEV ORF3 protein but not to ORF3 mutant with proline to leucine mutations in the PxYPMP motif. Rat HEV release was also decreased in Ras-associated binding 27A (Rab27A)- or hepatocyte growth factor-regulated tyrosine kinase substrate (Hrs)-depleted cells (to 20.1 % and 18.5 %, respectively). In addition, the extracellular rat HEV levels in the infected PLC/PRF/5 cells were increased after treatment with Bafilomycin A1 and decreased after treatment with GW4869. These results indicate that rat HEV utilizes multivesicular body (MVB) sorting for its release and that the exosomal pathway is required for rat HEV egress. A host protein alternative to Tsg101 that can bind to rat HEV ORF3 should be explored in further study.
  • Hiroshi Okano, Hiroki Asakawa, Satomi Tsuruga, Kenji Nose, Tomomasa Tochio, Hiroaki Kumazawa, Yoshiaki Isono, Hiroki Tanaka, Shimpei Matsusaki, Tomohiro Sase, Tomonori Saito, Katsumi Mukai, Akira Nishimura, Masaharu Takahashi, Hiroaki Okamoto
    Acta Hepatologica Japonica 61(6) 326-334 2020年  
  • Naoki Nakagawa, Tatsunori Nakano, Ryohei Sak-Aguchi, Toshitaka Fukui, Kunihiro Higuchi, Shigehito Nakashima, Satoshi Takaji, Miho Miyoshi, Shigeo Nagashima, Masaharu Takahashi, Shozo Watanabe, Yoshiyuki Takei, Hiroaki Okamoto
    Acta Hepatologica Japonica 61(5) 270-272 2020年  
  • Yohei Owada, Yukio Oshiro, Yuki Inagaki, Hiroshi Harada, Nobuhiro Fujiyama, Naoki Kawagishi, Takashi Yagisawa, Joichi Usui, Naotake Akutsu, Yoshihiro Itabashi, Kazuhide Saito, Yoshihiko Watarai, Naotsugu Ichimaru, Ryoichi Imamura, Miyaji Kyakuno, Kentaro Ide, Yuichi Shibuya, Yasuhiro Okabe, Minoru Ono, Konosuke Sasaki, Akira Shiose, Kazumasa Yamagishi, Hiroshi Ohnishi, Shigeo Nagashima, Masaharu Takahashi, Kenji Yuzawa, Hiroaki Okamoto, Nobuhiro Ohkohchi
    Transplantation 104(2) 437-444 2020年  査読有り
  • Shunji Watanabe, Naoki Morimoto, Kouichi Miura, Yoshinari Takaoka, Hiroaki Nomoto, Mamiko Tsukui, Norio Isoda, Hiroshi Ohnishi, Shigeo Nagashima, Masaharu Takahashi, Hiroaki Okamoto, Hironori Yamamoto
    HEPATOLOGY RESEARCH 49(5) 521-530 2019年5月  
  • Nakano T, Okano H, Takahashi M, Nagashima S, Shiraki K, Oya Y, Inoue H, Ohmori S, Tsukimoto M, Ishida S, Fujimoto S, Kobayashi M, Yamawaki M, Kumagai M, Ninomiya J, Maegawa T, Kojima Y, Araki J, Hamaoka S, Horiike S, Yoshimura H, Takeuchi K, Itoh K, Akachi S, Uraki S, Yamamoto N, Ogura S, Sugimoto K, Yoshikawa K, Hasegawa H, Iwasa M, Takei Y, Okamoto H
    Hepatology research : the official journal of the Japan Society of Hepatology 49(9) 1003-1014 2019年4月  査読有り
  • Naoto Sato, Shunji Watanabe, Kouichi Miura, Rie Goka, Naoki Morimoto, Yoshinari Takaoka, Hiroaki Nomoto, Mamiko Tsukui, Norio Isoda, Shigeo Nagashima, Masaharu Takahashi, Hiroaki Okamoto, Hironori Yamamoto
    INTERNAL MEDICINE 58(20) 2963-2968 2019年  
  • 中野 達徳, 岡野 宏, 西垣 洋一, 鈴木 祐介, 冨田 栄一, 小林 真, 山脇 真, 清水 省吾, 山下 晃司, 杉原 潤一, 高橋 和明, 新井 雅裕, 高橋 雅春, 長嶋 茂雄, 岡本 宏明
    肝臓 59(12) 700-703 2018年12月  査読有り
  • Tsutomu Nishizawa, Yuji Sugimoto, Tsutomu Takeda, Yuuji Kodera, Yumi Hatano, Masaharu Takahashi, Hiroaki Okamoto
    Virus Research 258 50-54 2018年10月15日  
  • Nishizawa Tsutomu, Sugimoto Yuji, Takeda Tsutomu, Kodera Yuuji, Hatano Yumi, Takahashi Masaharu, Okamoto Hiroaki
    VIRUS RESEARCH 256 183-191 2018年9月2日  査読有り
  • 清水 省吾, 山下 晃司, 杉原 潤一, 中野 達徳, 高橋 雅春, 長嶋 茂雄, 岡本 宏明
    肝臓 59(9) 497-500 2018年9月  査読有り
  • Putu Prathiwi Primadharsini, Mulyanto, I. Dewa Nyoman Wibawa, Joko Anggoro, Tsutomu Nishizawa, Masaharu Takahashi, Suljid Jirintai, Hiroaki Okamoto
    Archives of Virology 163(5) 1345-1349 2018年5月1日  査読有り
  • Tanggis, Tominari Kobayashi, Masaharu Takahashi, Suljid Jirintai, Tsutomu Nishizawa, Shigeo Nagashima, Takashi Nishiyama, Satoshi Kunita, Emiko Hayama, Takeshi Tanaka, Mulyanto, Hiroaki Okamoto
    Virus Research 249 16-30 2018年4月2日  査読有り
  • Tetsuro Sawata, Masashi Bando, Masayuki Nakayama, Naoko Mato, Hideaki Yamasawa, Masaharu Takahashi, Hiroaki Okamoto, Yukihiko Sugiyama
    Respiratory Investigation 56(2) 173-178 2018年3月1日  査読有り
  • Tatsunori Nakano, Hiroshi Okano, Yoichi Nishigaki, Yusuke Suzuki, Eiichi Tomita, Makoto Kobayashi, Makoto Yamawaki, Shogo Shimizu, Koji Yamashita, Jun-Ichi Sugihara, Kazuaki Takahashi, Masahiro Arai, Masaharu Takahashi, Shigeo Nagashima, Hiroaki Okamoto
    Acta Hepatologica Japonica 59(12) 700-703 2018年  
  • Shogo Shimizu, Koji Yamashita, Jun-Ichi Sugihara, Tatsunori Nakano, Masaharu Takahashi, Shigeo Nagashima, Hiroaki Okamoto
    Acta Hepatologica Japonica 59(9) 497-500 2018年  
  • Kosei Hashimoto, Kouichi Miura, Yoshinari Takaoka, Hiroaki Nomoto, Shunji Watanabe, Mamiko Tsukui, Naoki Morimoto, Norio Isoda, Shigeo Nagashima, Masaharu Takahashi, Hiroaki Okamoto, Hironori Yamamoto
    INTERNAL MEDICINE 57(21) 3099-3104 2018年  
  • Bira Tsatsralt-Od, Putu Prathiwi Primadharsini, Tsutomu Nishizawa, Hiroshi Ohnishi, Shigeo Nagashima, Masaharu Takahashi, Suljid Jirintai, Dulmaa Nyamkhuu, Hiroaki Okamoto
    JOURNAL OF MEDICAL VIROLOGY 90(1) 84-92 2018年1月  査読有り
  • Nakano T, Takahashi M, Takahashi K, Nagashima S, Suzuki Y, Nishigaki Y, Tomita E, Okano H, Oya Y, Shiraki K, Takase K, Sugimoto K, Koyama J, Mizuo H, Ikezawa K, Aikawa T, Arai M, Okamoto H
    Virology 513 146-152 2018年1月  査読有り
    Hepatitis E virus subtype 3f (HEV-3f) strains are usually isolated in Europe and Thailand. Recently, HEV-3f strains were detected from six acute hepatitis E patients in Japan, none of whom had a history of travel to endemic areas. We inferred the origin and transmission route of the six HEV-3f strains. A time-scaled phylogenetic tree of the six strains with reference strains was constructed using a Bayesian statistical inference framework. The time-scaled tree indicated that the six strains independently derived from similar European strains between 2008 and 2014. The pattern suggested recent inflow of multiple HEV-3f strains from Europe to Japan. Japan imports a substantial amount of pork from European countries every year. The emergence of acute hepatitis cases caused by HEV-3f strains in Japan, in patients with no history of travel abroad, might be influenced by the increased opportunities to consume pork products imported from European countries.
  • Shigeo Nagashima, Masaharu Takahashi, Tominari Kobayashi, Tanggis, Tsutomu Nishizawa, Takashi Nishiyama, Putu Prathiwi Primadharsini, Hiroaki Okamoto
    JOURNAL OF VIROLOGY 91(22) 2017年11月  査読有り
  • Tsutomu Nishizawa, Putu Prathiwi Primadharsini, Masashi Namikawa, Yuichi Yamazaki, Satoko Uraki, Hiroshi Okano, Shinichiro Horiike, Tatsunori Nakano, Shintaro Takaki, Manri Kawakami, Shigeo Nagashima, Masaharu Takahashi, Hiroaki Okamoto
    INFECTION GENETICS AND EVOLUTION 55 343-349 2017年11月  査読有り
  • Yokoyama K, Kumagai H, Takahashi M, Nagashima S, Okamoto H, Yamagata T
    Pediatr Int 59(9) 1010-1016 2017年9月  査読有り
  • Putu Prathiwi Primadharsini, Masao Miyake, Satoshi Kunita, Tsutomu Nishizawa, Masaharu Takahashi, Shigeo Nagashima, Tanggis, Hiroshi Ohnishi, Tominari Kobayashi, Takashi Nishiyama, Suljid Jirintai, Hiroaki Okamoto
    VIRUS RESEARCH 240 147-153 2017年8月  査読有り

MISC

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共同研究・競争的資金等の研究課題

 11