Measles virus infection of epitherial cells

• Project/Area Number: 22790445
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Single-year Grants
• Research Field: Virology
• Research Institution: National Institute of Infectious Diseases
• Principal Investigator: TAHARA Maino 国立感染症研究所, ウイルス第三部, 主任研究官 (10572109)
• Project Period (FY): 2010-04-01 – 2014-03-31
• Project Status: Completed (Fiscal Year 2013)
• Budget Amount: ¥3,770,000 (Direct Cost: ¥2,900,000、Indirect Cost: ¥870,000); Fiscal Year 2013: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000); Fiscal Year 2012: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000); Fiscal Year 2011: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000); Fiscal Year 2010: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
• Keywords: 麻疹ウイルス / ウイルス学 / ワクチン / 上皮細胞 / 極性上皮細胞 / 受容体

Research Abstract

Monoclonal antibodies (MAbs) recognizing distinct epitopes on the H protein were characterized using recombinant MVs. We identified the location of five epitopes on the H protein structure. Our data in the present study demonstrated that the H protein of MV possesses at least two conserved effective neutralizing epitopes. One, which is a previously recognized epitope, is located near the receptor-binding site (RBS), whereas the other epitope is located at the position distant from the RBS. MAb that recognizes this epitope interfered with the hemagglutinin-fusion (H-F) interaction. This epitope was suggested to play a key role for formation of a higher order of an H-F protein oligomeric structure. Our data also identified one nonconserved effective neutralizing epitope. This epitope has been masked by an N-linked sugar modification in some genotype MV strains.

Research Products

• [Journal Article] The host protease TMPRSS2 plays a major role for in vivo replication of emerging H7N9 and seasonal influenza viruses. (2014)
  • Author(s): Sakai K, Ami Y, Tahara M, Kubota T, Anraku M, Abe M, Nakajima N, Sekizuka T, Shirato K, Suzaki Y, Ainai A, Nakatsu Y, Kanou K, Nakamura K, Suzuki T, Komase K, Nobusawa E, Maenaka K, Kuroda M, Hasegawa H, Kawaoka Y, Tashiro M, Takeda M.
  • Journal Title: J Virol Volume: 印刷中
  • Peer Reviewed
• [Journal Article] The receptor-binding site of the measles virus hemagglutinin protein itself constitutes a conserved neutralizing epitope (2013)
  • Author(s): Tahara M, Ohno S, Sakai K, Ito Y, Fukuhara H, Komase K, Brindley MA, Rota PA, Plemper RK, Maenaka K, Takeda M.
  • Journal Title: J Virol. Volume: 87巻 Issue: 6 Pages: 3583-3586
  • DOI: 10.1128/jvi.03029-12
  • Peer Reviewed
• [Journal Article] Functional and structural characterization of neutralizing epitopes of measles virus hemagglutinin protein (2013)
  • Author(s): Tahara M, Ito Y, Brindley MA, Ma X, He J, Xu S, Fukuhara H, Sakai K, Komase K, Rota PA, Plemper RK, Maenaka K, Takeda M.
  • Journal Title: J Virol. Volume: 87巻 Issue: 1 Pages: 666-675
  • DOI: 10.1128/jvi.02033-12
  • Peer Reviewed
• [Journal Article] The MyD88 pathway in plasmacytoide and CO4+ dendritic cells primarily triggers type I interferon production against measles virus in a mouse infection model. (2013)
  • Author(s): Hiromi Takaki, et al.
  • Journal Title: Journal of Immunolog Volume: 191 Issue: 9 Pages: 4740-4747
  • DOI: 10.4049/jimmunol.1301744
  • Peer Reviewed
• [Journal Article] TMPRSS2 is an activating protease for respiratory parainfluenza viruses. (2013)
  • Author(s): Abe M, Tahara M, Sakai K, Yamaguchi H, Kanou K, Shirato K, Kawase M, Noda M, Kimura H, Matsuyama S, Fukuhara H, Mizuta K, Maenaka K, Ami Y, Esumi M, Kato A, Takeda M.
  • Journal Title: J Virol Volume: 87 Issue: 21 Pages: 11930-11935
  • DOI: 10.1128/jvi.01490-13
  • Peer Reviewed
• [Journal Article] Canine distemper virus associated with a lethal outbreak in monkeys can readily adapt to use human receptors. (2013)
  • Author(s): Sakai K, Yoshikawa T, Seki F, Fukushi S, Tahara M, Nagata N, Ami Y, Mizutani T, Kurane I, Yamaguchi R, Hasegawa H, Saijo M, Komase K, Morikawa S, Takeda M.
  • Journal Title: J Virol Volume: 87 Issue: 12 Pages: 7170-7175
  • DOI: 10.1128/jvi.03479-12
  • Peer Reviewed
• [Journal Article] Wild-Type Measles Virus is Intrinsically Dual-Tropic (2012)
  • Author(s): Takeda M, Tahara M, Nagata N,Seki F
  • Journal Title: Front Microbiol Volume: 2巻 Pages: 279-279
  • DOI: 10.3389/fmicb.2011.00279
  • Peer Reviewed
• [Journal Article] 野生型麻疹ウイルスの二つのレセプター (2011)
  • Author(s): 田原舞乃、竹田誠
  • Journal Title: ウイルス Volume: 61 Pages: 249-256
  • NAID: 10030578488
• [Presentation] 麻疹ウイルスの抗原性の安定性は強固に保証されている (2013)
  • Author(s): 竹田誠, 田原舞乃, 駒瀬勝啓
  • Organizer: 第17回日本ワクチン学会
  • Place of Presentation: 三重
  • Year and Date: 2013-11-30
• [Presentation] 受容体結合領域を含む複数の主要エピトープを変化させた麻疹ウイルスの解析 (2013)
  • Author(s): 田原舞乃, 酒井宏治, 駒瀬勝啓, 前仲勝実, 竹田誠
  • Organizer: 第61回日本ウイルス学会学術集会
  • Place of Presentation: 神戸
• [Presentation] 受容体結合領域を含む複数の主要エピトープを変化させた麻疹ウイルスの解析 (2013)
  • Author(s): 田原舞乃、酒井宏治、駒瀬勝啓、前仲勝実、竹田誠
  • Organizer: 第61回日本ウイルス学会学術集会
  • Place of Presentation: 神戸国際会議場
• [Presentation] 麻疹ウイルスの抗原性の安定性は強固に保証されている (2013)
  • Author(s): 田原舞乃、酒井宏治、駒瀬勝啓、前仲勝実、竹田誠
  • Organizer: 第17回 日本ワクチン学会学術集会
  • Place of Presentation: 三重県総合文化センター
• [Presentation] Importance of the P2 and P3 residues of fusion proteins of respiratory viruses for their proteolytic activation by TMPRSS2 (2013)
  • Author(s): Maino Tahara, Masako Abe, Kouji Sakai, Kazuya Shirato, Kazuhiko Kanou1, Shutoku Matsuyama1, Hideo Fukuhara, Katsumi Maenaka, Yasushi Ami, Mariko Esumi, Atsushi Kato, Makoto Takeda
  • Organizer: NSV Meeting 2013
  • Place of Presentation: Granada, Spain
• [Presentation] High potential of canine distemper virus in the ability to use macaca and human receptors (2013)
  • Author(s): Kouji Sakai, Fumio Seki, Maino Tahara, Noriyuki Otsuki, Yasushi Ami, Ryoji Yamaguchi, Masayuki Saijo, Katsuhiro Komase, Shigeru Morikawa, Makoto Takeda
  • Organizer: NSV Meeting 2013
  • Place of Presentation: Granada, Spain
• [Presentation] 犬ジステンパーウイルスのヒトSLAM利用能獲得に必要な変異 (2013)
  • Author(s): 酒井宏治、關文緒、網康至、染谷健二、田原舞乃、大槻紀之、西條政幸、森川茂、山口良二、駒瀬勝啓、竹田誠
  • Organizer: 第61回日本ウイルス学会学術集会
  • Place of Presentation: 神戸国際会議場
• [Presentation] 麻疹ウイルスの単一血清型の分子機構ならびにワクチン効果減弱の可能性について (2012)
  • Author(s): 田原舞乃, 駒瀬勝啓, 竹田誠
  • Organizer: 第1回Negative Strand Virus- JAPAN Symposium
  • Place of Presentation: 長崎
  • Year and Date: 2012-01-21
• [Presentation] 麻疹ウイルスの単一血清型の分子機構ならびにワクチン効果減弱の可能性について (2012)
  • Author(s): 田原舞乃、駒瀬勝啓、竹田誠
  • Organizer: 第1回Negative Strand Virus-JAPAN Symposium
  • Place of Presentation: 長崎
  • Year and Date: 2012-01-21
• [Presentation] A structural and biochemical basis for the single serotype nature of MV (2012)
  • Author(s): Tahara M, Ito Y, Brindley MA, Ma XM, He JL, Xu ST, Fukuhara H, Sakai K, Ohno S, Komase K, Rota PA, Plemper RK, Maenaka K, and Takeda M
  • Organizer: The 11th Awaji International Forum on Infection and Immunity
  • Place of Presentation: Hyogo, Japan
• [Presentation] Virological, Structural and Molecular Bases for the Unchanged Antigenicity of Measles Virus (2012)
  • Author(s): Tahara M, Ito Y, Brindley MA, Ma XM, He JL, Xu ST, Fukuhara H, Sakai K, Ohno S, Komase K, Rota PA, Plemper RK, Maenaka K, and Takeda M.
  • Organizer: Osong Symposium on Infectious Disease
  • Place of Presentation: 韓国
• [Presentation] Structural and functional constraints on the measles virus hemagglutinin protein prevent escape from neutralization (2012)
  • Author(s): Takeda M, Tahara M, Ito Y, Brindley MA, Fukuhara H, Komase K, Yanagi Y, Rota PA, Plemper RK, Maenaka K.
  • Organizer: The 34th Naito Conference
  • Place of Presentation: 札幌
• [Presentation] 麻疹ウイルス単一血清型決定の分子基盤 (2012)
  • Author(s): 田原舞乃, Melinda A. Brindley, 福原秀雄, 酒井宏治, 大野真治, 駒瀬勝啓, Paul A. Rota , Richard K. Plemper, 前仲勝実, 竹田誠
  • Organizer: 第60回日本ウイルス学会学術集会
  • Place of Presentation: 大阪
• [Presentation] 麻疹ウイルス H タンパク質全エピトープの詳細な解析 (2012)
  • Author(s): 田原舞乃, 駒瀬勝啓, 竹田誠
  • Organizer: 第16回日本ワクチン学会
  • Place of Presentation: 横浜
• [Presentation] A structural and biochemical basis for the single serotype nature of MV (2012)
  • Author(s): Maino Tahara
  • Organizer: The 11th Awaji International Forum on Infection and Immunity
  • Place of Presentation: 兵庫県
• [Presentation] 麻疹ウイルス単一血清型決定の分子基盤 (2012)
  • Author(s): 田原舞乃
  • Organizer: 第60回日本ウイルス学会学術集会
  • Place of Presentation: 大阪府
• [Presentation] 麻疹ウイルスHタンパク質全エピトープの詳細な解析 (2012)
  • Author(s): 田原舞乃
  • Organizer: 第16回日本ワクチン学会
  • Place of Presentation: 横浜市
• [Presentation] 麻疹ウイルスの単一血清型の分子機構ならびにワクチン効果減弱の可能性について (2011)
  • Author(s): 田原舞乃, 駒瀬勝啓, 竹田誠
  • Organizer: 第15回日本ワクチン学会
  • Place of Presentation: 東京
  • Year and Date: 2011-12-11
• [Presentation] The SI strain of measles virus derived from an SSPE patient exhibits alterd receptor specificity and reduced membrane fusion activity (2011)
  • Author(s): Fumio Seki, Yuichiro Nakatsu, Kenji Someya, Maino Tahara, Katsuhiro Komase, Makoto Takeda
  • Organizer: International Union of Microbiological Societies Congresses
  • Place of Presentation: 札幌
  • Year and Date: 2011-09-15
• [Presentation] Identification of conserved neutralizing epitopes of the measles virus hemagglutinin protein located in proximity and distal to the receptor-binding site (2011)
  • Author(s): Maino Tahara, Katsuhiro Komase, Xue-Min Ma, Ji-Lan He, Yusuke Yanagi, Katsumi Maenaka, Paul A. Rota, and Makoto Takeda
  • Organizer: International Union of Microbiological Societies Congresses
  • Place of Presentation: 札幌
  • Year and Date: 2011-09-13
• [Presentation] CONSERVED AND VARIABLE ANTIGENIC SITES ON THE MEASLES VIRUS HEMAGGLUTININ PROTEIN (2011)
  • Author(s): Maino Tahara, Katsuhiro Komase, Yusuke Yanagi, Katsumi Maenaka, Paul A. Rota, Makoto Takeda
  • Organizer: American society for virology 30th annual meeting
  • Place of Presentation: ミネアポリス(アメリカ)
  • Year and Date: 2011-07-18
• [Presentation] CONSERVED AND VARIABLE ANTIGENIC SITES ON THE MEASLES VIRUS HEMAGGLUTININ PROTEIN (2011)
  • Author(s): Maino Tahara, Katsuhiro Komase, Yusuke Yanagi, Katsumi Maenaka, Paul A.Rota, Makoto Takeda
  • Organizer: American society for virology 30^<th> annual meeting
  • Place of Presentation: ミネアポリス(アメリカ)
  • Year and Date: 2011-07-18
• [Presentation] Antigenic Determinants of Measles Virus Hemagglutinin associated with single serotype (2011)
  • Author(s): Maino Tahara, Katsuhiro Komase, Xue-Min Ma, Ji-Lan He, Yusuke Yanagi, Katsumi Maenaka, Paul A. Rota and Makoto Takeda
  • Organizer: Measles virus mini-symposium
  • Place of Presentation: ロチェスター(アメリカ)
  • Year and Date: 2011-07-15
• [Presentation] 麻疹ウイルスの抗原性変化 (2010)
  • Author(s): 田原舞乃
  • Organizer: 第14回日本ワクチン学会
  • Place of Presentation: 東京
  • Year and Date: 2010-12-11
• [Presentation] 麻疹ウイルス主要表面抗原Hタンパク質の抗原性変化 (2010)
  • Author(s): 田原舞乃
  • Organizer: 第58回日本ウイルス学会学術集会
  • Place of Presentation: 徳島
  • Year and Date: 2010-11-08
• [Presentation] ANTIGENIC VARIATIONS AMONG CURRENTLY CIRCULATING WILD-TYPE MEASLES VIRUS STRAINS (2010)
  • Author(s): 田原舞乃
  • Organizer: 第4回ATLANTA PARAMYXER
  • Place of Presentation: アトランタ(アメリカ)
  • Year and Date: 2010-10-29
• [Presentation] ANTIGENIC VARIATIONS AMONG CURRENTLY CIRCUILATING WILD-TYPE-MEASLES VIRUS STRAINS (2010)
  • Author(s): 田原舞乃
  • Organizer: 2010 Negative Strand Virus Meeting
  • Place of Presentation: ブルージュ(ベルギー)
  • Year and Date: 2010-06-25
• [Book] 新編ウイルスの今日的意味(編者 : 柳雄介, 堤裕幸) (2012)
  • Author(s): 田原舞乃, 染谷健司, 竹田誠
  • Publisher: 医薬ジャーナル社
• [Book] 新編ウイルスの今日的意味 (2012)
  • Author(s): 柳雄介
  • Total Pages: 235
  • Publisher: 医薬ジャーナル社
• [Book] ウイルスのリバースジェネティクス (2010)
  • Author(s): 田原舞乃, 染谷健司, 竹田誠
• [Book] 化学療法の領域 (2010)
  • Author(s): 田原舞乃
  • Total Pages: 6
  • Publisher: ウイルスのリバースジェネティクス