Research on release mechanism, genome mutations and cellular receptor of hepatitis E virus (HEV) using cell culture systems for HEV

• Project/Area Number: 22390090
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Virology
• Research Institution: Jichi Medical University
• Principal Investigator: OKAMOTO Hiroaki 自治医科大学, 医学部, 教授 (30177092)
• Co-Investigator(Kenkyū-buntansha): NAGASHIMA Shigeo 自治医科大学, 医学部, 講師 (60433116) ; TAKAHASHI Masaharu 自治医科大学, 医学部, 講師 (70326841) ; KOBAYASHI Tominari 自治医科大学, 医学部, 助教 (00634164) ; 田中 利典 自治医科大学, 医学部, 講師 (30146154)
• Project Period (FY): 2010 – 2012
• Project Status: Completed (Fiscal Year 2012)
• Budget Amount: ¥18,330,000 (Direct Cost: ¥14,100,000、Indirect Cost: ¥4,230,000); Fiscal Year 2012: ¥6,110,000 (Direct Cost: ¥4,700,000、Indirect Cost: ¥1,410,000); Fiscal Year 2011: ¥5,590,000 (Direct Cost: ¥4,300,000、Indirect Cost: ¥1,290,000); Fiscal Year 2010: ¥6,630,000 (Direct Cost: ¥5,100,000、Indirect Cost: ¥1,530,000)
• Keywords: E型肝炎ウイルス / 感染培養系 / 感染性 cDNA クローン / 感受性細胞 / 吸着 / 細胞レセプター候補分子 / 感染性cDNAクローン / 劇症肝炎 / ゲノム変異 / ORF3蛋白質 / PSAPモチーフ / Tsg101 / 放出機構 / MVB sorting

Research Abstract

Utilizing our efficient cell culture systems for hepatitis E virus (HEV), we elucidated that the ORF3 protein with an intact PSAP motif as well as Tsg101 and Vps4 as host factors are essential for the formation and release of membrane-associated HEV parti

Research Products

• [Journal Article] Frequent detection and characterization of hepatitis E virus variants in wild rats (Rattus rattus) in Indonesia (2013)
  • Author(s): Mulyanto, Depamede SN, Sriasih M, Takahashi M, Nagashima S, Jirintai S, Nishizawa T, Okamoto H
  • Journal Title: Arch Virol Volume: 158(1) Pages: 87-96
  • Peer Reviewed
• [Journal Article] Culture systems for hepatitis E virus (2013)
  • Author(s): Okamoto H.
  • Journal Title: J Gastroenterol Volume: 48(2) Pages: 147-58
  • NAID: 10031156300
  • Peer Reviewed
• [Journal Article] strains isolated from an acute hepatitis patient and a wild boar in Mie, Japan (2013)
  • Journal Title: Hepatol Res Volume: 印刷中 Issue: 6 Pages: 694-699
  • DOI: 10.1111/hepr.12155
  • Peer Reviewed
• [Journal Article] Features of hepatitis E virus infection in humans and animals in Japan (2013)
  • Author(s): Takahashi M, Okamoto H
  • Journal Title: Hepatol Res Volume: 44 Issue: 1 Pages: 43-58
  • DOI: 10.1111/hepr.12175
  • Peer Reviewed
• [Journal Article] Culture systems for hepatitis E virus (2013)
  • Author(s): Okamoto H
  • Journal Title: Journal of Gastroenterology Volume: 48 Issue: 2 Pages: 147-158
  • DOI: 10.1007/s00535-012-0682-0
  • NAID: 10031156300
  • Peer Reviewed
• [Journal Article] Frequent detection and characterization of hepatitis E virus variants in wild rats (Rattus rattus) in Indonesia (2013)
  • Author(s): Mulyanto
  • Journal Title: Archives of Virology Volume: 158 Issue: 1 Pages: 87-96
  • DOI: 10.1007/s00705-012-1462-0
  • Peer Reviewed
• [Journal Article] 抗肝炎ウイルス薬(A型肝炎、E型肝炎) (2013)
  • Author(s): 岡本宏明
  • Journal Title: 臨床と微生物 Volume: 40 Pages: 57-63
• [Journal Article] Icteric acute hepatitis E with no response of immunoglobulin M class anti-hepatitis E virus antibody (2012)
  • Author(s): Takikawa Y, Miyamoto Y, Onodera M, Kuroda H, Kasai K, Miyasaka A, Takahashi M, Okamoto H, Suzuki K
  • Journal Title: Hepatol Res Volume: 42(11) Pages: 1146-9
  • Peer Reviewed
• [Journal Article] Molecular analysis of hepatitis E virus from farm rabbits in Inner Mongolia, China and its successful propagation in A549 and PLC/PRF/5 cells (2012)
  • Author(s): D, Mulyanto, Takahashi M, Nagashima S, Kobayashi T, Nishizawa T, Okamoto H
  • Journal Title: Virus Res Volume: 170(1-2) Pages: 126-37
  • Peer Reviewed
• [Journal Article] Molecular epidemiology and genetic history of European-type genotype 3 hepatitis E virus indigenized in the central region of Japan (2012)
  • Author(s): Nakano T, Okano H, Kobayashi M, Ito K, Ohmori S, Nomura T, Kato H, Ayada M, Nakano Y, Akachi S, Sugimoto K, Fujita N, Shiraki K, Takei Y, Takahashi M, Okamoto H
  • Journal Title: Infect Genet Evol Volume: 12(7) Pages: 1524-34
  • Peer Reviewed
• [Journal Article] New findings regarding the epidemic history and population dynamics of Japan-indigenous genotype 3 hepatitis E virus inferred by molecular evolution (2012)
  • Author(s): Nakano T, Takahashi K, Pybus OG, Hashimoto N, Kato H, Okano H, Kobayashi M, Fujita N, Shiraki K, Takei Y, Ayada M, Arai M, Okamoto H, Mishiro S.
  • Journal Title: Liver Int Volume: 32(4) Pages: 675-88
  • Peer Reviewed
• [Journal Article] A549 and PLC/PRF/5 cells can support the efficient propagation of swine and wild boar hepatitis E virus (HEV) strains: demonstration of HEV infectivity of porcine liver sold as food (2012)
  • Author(s): Takahashi H, Tanaka T, Jirintai S, Nagashima S, Takahashi M, Nishizawa T, Mizuo H, Yazaki Y, Okamoto H
  • Journal Title: Arch Virol Volume: 157(2) Pages: 235-46
  • Peer Reviewed
• [Journal Article] Icteric acute hepatitis E with no response of immunoglobulin M class anti-hepatitis E virus antibody (2012)
  • Author(s): Takikawa Y
  • Journal Title: Hepatology Research Volume: 42 Issue: 11 Pages: 1146-1149
  • DOI: 10.1111/j.1872-034x.2012.01023.x
  • Peer Reviewed
• [Journal Article] Molecular analysis of hepatitis E virus from farm rabbits in Inner Mongolia, China and its successful propagation in A549 and PLC/PRF/5 cells (2012)
  • Author(s): Jirintai S
  • Journal Title: Virus Research Volume: 170 Issue: 1-2 Pages: 126-137
  • DOI: 10.1016/j.virusres.2012.09.015
  • Peer Reviewed
• [Journal Article] Molecular epidemiology and genetic history of European-type genotype 3 hepatitis E virus indigenized in the central region of Japan (2012)
  • Author(s): Nakano T
  • Journal Title: Infection, Genetics and Evolution Volume: 12 Issue: 7 Pages: 1524-1534
  • DOI: 10.1016/j.meegid.2012.06.002
  • Peer Reviewed
• [Journal Article] New findings regarding the epidemic history and population dynamics of Japan-indigenous genotype 3 hepatitis E virus inferred by molecular evolution (2012)
  • Author(s): Nakano T
  • Journal Title: Liver International Volume: 32 Issue: 4 Pages: 675-688
  • DOI: 10.1111/j.1478-3231.2011.02728.x
  • Peer Reviewed
• [Journal Article] E型肝炎ウイルス培養系 (2012)
  • Author(s): 岡本宏明
  • Journal Title: 化学療法の領域 Volume: 28 Pages: 114-123
• [Journal Article] E型肝炎の現状と今後の戦略 (2012)
  • Author(s): 岡本宏明
  • Journal Title: 日本医事新報 Volume: 4621 Pages: 71-77
  • NAID: 40019481043
• [Journal Article] E型肝炎ウイルス感染の現状と対策 (2012)
  • Author(s): 岡本宏明
  • Journal Title: 血液事業 Volume: 35 Pages: 228-229
• [Journal Article] A549 and PLC/PRF/5 cells can support the efficient propagation of swine and wild boar hepatitis E virus (HEV) strains : demonstration of HEV infectivity of porcine liver sold as food (2012)
  • Author(s): Takahashi H
  • Journal Title: Archives of Virology Volume: 157 Issue: 2 Pages: 235-246
  • DOI: 10.1007/s00705-011-1153-2
  • Peer Reviewed
• [Journal Article] 2009年秋に札幌圏で発生したE型肝炎小流行の臨床的・ウイルス学的・分子疫学的解析 (2012)
  • Author(s): 小関至
  • Journal Title: 肝臓 Volume: 53 Pages: 78-89
  • Peer Reviewed
• [Journal Article] Tumour susceptibility gene 101 and the vacuolar protein sorting pathway are required for the release of hepatitis E virions. (2011)
  • Author(s): Nagashima S, Takahashi M, Jirintai S, Tanaka T, Nishizawa T, Yasuda J, Okamoto H.
  • Journal Title: J Gen Virol Volume: 92(Pt 12) Pages: 2838-48
  • Peer Reviewed
• [Journal Article] A nationwide survey of hepatitis E virus (HEV) infection in wild boars in Japan: identification of boar HEV strains of genotypes 3 and 4 and unrecognized genotypes (2011)
  • Author(s): Sato Y, Sato H, Naka K, Furuya S, Tsukiji H, Kitagawa K, Sonoda Y, Usui T, Sakamoto H, Yoshino S, Shimizu Y, Takahashi M, Nagashima S, Jirintai, Nishizawa T, Okamoto H.
  • Journal Title: Arch Virol Volume: 156(8) Pages: 1345-58
  • Peer Reviewed
• [Journal Article] Hepatitis E virus cell culture models (2011)
  • Author(s): Okamoto H
  • Journal Title: Virus Res Volume: 161(1) Pages: 65-77
  • Peer Reviewed
• [Journal Article] Efficient cell culture systems for hepatitis E virus strains in feces and circulating blood (2011)
  • Author(s): Okamoto H
  • Journal Title: Rev Med Virol Volume: 21(1) Pages: 18-31
  • Peer Reviewed
• [Journal Article] Analysis of the full-length genome of a hepatitis E virus isolate obtained from a wild boar in Japan that is classifiable into a novel genotype (2011)
  • Author(s): Takahashi M, Nishizawa T, Sato H, Sato Y, Jirintai, Nagashima S, Okamoto H
  • Journal Title: J Gen Virol Volume: 92(Pt 4) Pages: 902-8
  • Peer Reviewed
• [Journal Article] A PSAP motif in the ORF3 protein of hepatitis E virus is necessary for virion release from infected cells (2011)
  • Author(s): Nagashima S, Takahashi M, Jirintai, Tanaka T, Yamada K, Nishizawa T, Okamoto H
  • Journal Title: J Gen Virol Volume: 92(Pt 2) Pages: 269-78
  • Peer Reviewed
• [Journal Article] Analysis of the full-length genome of a hepatitis E virus isolate obtained from a wild boar in Japan that is classifiable into a novel genotype (2011)
  • Author(s): Takahashi M
  • Journal Title: Journal of General Virology Volume: 92 Issue: 4 Pages: 902-908
  • DOI: 10.1099/vir.0.029470-0
  • Peer Reviewed
• [Journal Article] Tumour susceptibility gene 101 and the vacuolar protein sorting pathway are required for the release of hepatitis E virions (2011)
  • Author(s): Nagashima S
  • Journal Title: Journal of General Virology Volume: 92 Issue: 12 Pages: 2838-2848
  • DOI: 10.1099/vir.0.035378-0
  • Peer Reviewed
• [Journal Article] A nationwide survey of hepatitis E virus (HEV) infection in wild boars in Japan : identification of boar HEV strains of genotypes 3 and 4 and unrecognized genotypes (2011)
  • Author(s): Sato Y
  • Journal Title: Archives of Virology Volume: 156 Issue: 8 Pages: 1345-1358
  • DOI: 10.1007/s00705-011-0988-x
  • Peer Reviewed
• [Journal Article] Hepatitis E virus cell culture models (2011)
  • Author(s): Okamoto H
  • Journal Title: Virus Research Volume: 161 Pages: 65-77
  • Peer Reviewed
• [Journal Article] 北海道東部の釧路市および根室市におけるE型肝炎ウイルス感染の疫学調査感染の地域差と食文化の相違について (2011)
  • Author(s): 田辺利男
  • Journal Title: 肝臓 Volume: 52 Pages: 567-574
  • Peer Reviewed
• [Journal Article] 三重県内で発生した稀な3型(ヨーロッパ型)E型肝炎ウイルスによる散発性急性肝炎の4症例 (2011)
  • Author(s): 岡野宏
  • Journal Title: 肝臓 Volume: 52 Pages: 295-302
  • Peer Reviewed
• [Journal Article] E型肝炎ウイルスのウイルス学的特徴 (2011)
  • Author(s): 岡本宏明
  • Journal Title: 日本臨床 Volume: 69 Pages: 579-587
• [Journal Article] Efficient cell culture systems for hepatitis E virus strains in feces and circulating blood. (2011)
  • Author(s): Okamoto H
  • Journal Title: Reviews in Medical Virology Volume: 21 Pages: 18-31
  • Peer Reviewed
• [Journal Article] A PSAP motif in the ORF3 protein of hepatitis E virus is necessary for virion release from infected cells. (2011)
  • Author(s): Nagashima S
  • Journal Title: Journal of General Virology Volume: 92 Pages: 269-278
  • Peer Reviewed
• [Journal Article] E型肝炎の現況 (2011)
  • Author(s): 岡本宏明
  • Journal Title: 綜合臨牀 Volume: 60 Pages: 95-101
  • NAID: 10018198977
• [Journal Article] Molecular and serological survey of hepatitis E virus infection among domestic pigs in Inner Mongolia (2010)
  • Author(s): Jinshan, Jirintai, Manglai D, Takahashi M, Nagashima S, Okamoto H
  • Journal Title: China. Arch Virol Volume: 155(8) Pages: 1217-26
  • Peer Reviewed
• [Journal Article] Hepatitis E Virus (HEV) strains in serum samples can replicate efficiently in cultured cells despite the coexistence of HEV antibodies: characterization of HEV virions in blood circulation (2010)
  • Author(s): Takahashi M, Tanaka T, Takahashi H, Hoshino Y, Nagashima S, Jirintai, Mizuo H, Yazaki Y, Takagi T, Azuma M, Kusano E, Isoda N, Sugano K, Okamoto H.
  • Journal Title: J Clin Microbiol Volume: 48(4) Pages: 1112-25
  • Peer Reviewed
• [Journal Article] A nationwide survey of hepatitis E virus infection in the general population of Japan (2010)
  • Author(s): Takahashi M, Tamura K, Hoshino Y, Nagashima S, Yazaki Y, Mizuo H, Iwamoto S, Okayama M, Nakamura Y, Kajii E, Okamoto H.
  • Journal Title: J Med Virol Volume: 82(2) Pages: 271-81
  • Peer Reviewed
• [Journal Article] Hepatitis E Virus(REV)strains in serum samples can replicate efficiently incultured cells despite the coexistence of HEV antibodies : characterization of HEV virions in blood circulation. (2010)
  • Author(s): Takahashi M
  • Journal Title: Journal of Clinical Microbiology Volume: 48 Pages: 1112-1125
  • Peer Reviewed
• [Journal Article] Molecular and serological survey of hepatitis E virus infection among domestic pigs in Inner Mongolia, China. (2010)
  • Author(s): Jinshan
  • Journal Title: Archives of Virology Volume: 155 Pages: 1217-1226
  • Peer Reviewed
• [Journal Article] E型肝炎ウイルスの感染培養系 (2010)
  • Author(s): 岡本宏明
  • Journal Title: ウイルス Volume: 60 Pages: 93-104
  • NAID: 10027049135
• [Journal Article] E型肝炎ウイルス感染 (2010)
  • Author(s): 岡本宏明
  • Journal Title: 治療学 Volume: 44 Pages: 974-977
• [Journal Article] E型肝炎をめぐって-診断法と感染培養系の確立と基礎・臨床への応用- (2010)
  • Author(s): 岡本宏明
  • Journal Title: Minophagen Medical Review Volume: 55 Pages: 207-218
• [Journal Article] A high genomic similarity between European type hepatitis E virus subgenotype 3e Jirintai S, Jinshan, Tanggis, Manglai 18. strains isolated from an acute hepatitis patient and a wild boar in Mie, Japan
  • Author(s): Okano H, Nakano T, Sugimoto K, Takahashi K, Nagashima S, Takahashi M, Arai M, Okamoto H
  • Journal Title: Jinshan, Tanggis, Manglai
• [Presentation] シンポジウム「E 型肝炎ウイルスについての最近の知見」 (2012)
  • Author(s): 岡本宏明
  • Organizer: 第60回日本ウイルス学会学術集会
  • Place of Presentation: 大阪市
  • Year and Date: 2012-11-13
• [Presentation] 特別講演「経口肝炎ウイルス:最近の知見」 (2012)
  • Author(s): 岡本宏明
  • Organizer: 第60回日本輸血細胞治療学会総会
  • Place of Presentation: 郡山市
  • Year and Date: 2012-05-25
• [Presentation] Culture systems for hepatitis E virus (2012)
  • Author(s): Okamoto, H.
  • Organizer: The 3rd International Forum of the 98th General Meeting of the Japanese Society of Gastroenterology
  • Place of Presentation: Tokyo
  • Year and Date: 2012-04-21
• [Presentation] 培養細胞から放出されたE型肝炎ウイルスの粒子表面に存在する膜成分の抗原性の解析 (2012)
  • Author(s): 長嶋茂雄
  • Organizer: 第60回日本ウイルス学会学術集会
  • Place of Presentation: 大阪国際会議場(大阪市)
• [Presentation] 経口肝炎ウイルス：最近の知見 (2012)
  • Author(s): 岡本宏明
  • Organizer: 第60回日本輸血細胞治療学会総会
  • Place of Presentation: ホテルハマツ(郡山市)
  • Invited
• [Presentation] 輸血によるウイルス感染の更なる減少を目指して (2012)
  • Author(s): 岡本宏明
  • Organizer: 第36回日本血液事業学会総会
  • Place of Presentation: 仙台国際センター(仙台市)
  • Invited
• [Presentation] E型肝炎ウイルスについての最近の知見 (2012)
  • Author(s): 岡本宏明
  • Organizer: 第60回日本ウイルス学会学術集会
  • Place of Presentation: 大阪国際会議場(大阪市)
  • Invited
• [Presentation] E型肝炎ウイルス感染の現状と対策 (2011)
  • Author(s): 岡本宏明
  • Organizer: 第35回日本血液事業学会総会
  • Place of Presentation: 浦和市
  • Year and Date: 2011-10-23
• [Presentation] Tsg101 and vacuolar protein sorting pathway are required for virion release of hepatitis E virus (2011)
  • Author(s): Nagashima S
  • Organizer: 14^<th> International Congress of Virology
  • Place of Presentation: 札幌市
  • Year and Date: 2011-09-13
• [Presentation] Tsg101 and vacuolar protein sorting pathway are required for virion release of hepatitis E virus (2011)
  • Author(s): Nagashima, S., Takahashi, M., Jirintai, Tanaka, T., Nishizawa, T., Yasuda J, Okamoto, H
  • Organizer: XV International Congress of Virology
  • Place of Presentation: Sapporo
• [Presentation] E型肝炎ウイルスのORF3蛋白質に認められるPSAPチーフのウイルス放出における機能解析 (2010)
  • Author(s): 長嶋茂雄
  • Organizer: 第56回日本ウイルス学会学術集会
  • Place of Presentation: 徳島市
  • Year and Date: 2010-11-09
• [Presentation] 肝炎ウイルスと肝炎重症化(劇症化) (2010)
  • Author(s): 岡本宏明
  • Organizer: 第36回日本急性肝不全研究会
  • Place of Presentation: 山形市
  • Year and Date: 2010-05-26
• [Book] Ninth Report of the International Committee on Taxonomy of Viruses (2011)
  • Author(s): Meng XJ
  • Publisher: Elsevier
• [Book] 肝・胆道系症候群(第2版)その他の肝・胆道系疾患を含めてI肝臓編(上) (2010)
  • Author(s): 高橋雅春(共著)
  • Publisher: 日本臨牀社
• [Book] 症例から学ぶウイルス肝炎の治療戦略 (2010)
  • Author(s): 岡本宏明(共著)
  • Publisher: 診断と治療社