A omputational study on the intermolecular interaction between influenza virus hemagglutinin and a monoclonal antibody

• Project/Area Number: 23780305
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Applied veterinary science
• Research Institution: Hokkaido University
• Principal Investigator: IGARASHI Manabu 北海道大学, 人獣共通感染症リサーチセンター, 特任助教 (10374240)
• Project Period (FY): 2011 – 2012
• Project Status: Completed (Fiscal Year 2013)
• Budget Amount: ¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000); Fiscal Year 2012: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2011: ¥2,990,000 (Direct Cost: ¥2,300,000、Indirect Cost: ¥690,000)
• Keywords: インフルエンザ / ウイルス / 計算科学 / 分子動力学 / 抗体 / 分子動力学シミュレーション / 分子間相互作用 / 抗原変異 / フラグメント分子軌道法 / 感染症 / 生体生命情報学 / 分子シミュレーション / 分子動力学計算

Research Abstract

Influenza A virus is a zoonotic pathogen that is transmitted from animals to humans. This virus has two surface glycoproteins, hemagglutinin (HA) and neuraminidase. The HA of human influenza virus is the major target of antibodies that neutralize viral infectivity. Some amino acid substitutions in the antigenic epitope on the HA could decrease the interaction between HA and antibodies, leading to generate the antigenic variants with a novel antigenic structure of HA. To understand how amino acid substitutions affect the changes of the HA antigenic structure, we computationally analyzed the three-dimensional structures of HA in complex with monoclonal antibody.

Research Products

• [Journal Article] Antiviral activity of stachyflin on influenza A viruses of different hemagglutinin subtypes (2013)
  • Author(s): Motohashi Y, Igarashi M, Okamatsu M, Noshi T, Sakoda Y, Yamamoto N, Ito K, Yoshida R, Kida H
  • Journal Title: Virol J Volume: 10 Issue: 1 Pages: 118-118
  • DOI: 10.1186/1743-422x-10-118
  • NAID: 120005323601
  • Peer Reviewed
• [Journal Article] Resampling nucleotide sequences with closest-neighbor trimming and its comparison to other methods (2013)
  • Author(s): Yonezawa K, Igarashi M, Ueno K, Takada A, Ito K
  • Journal Title: PLoS One Volume: 8 (10) Issue: 2 Pages: e57684-e57684
  • DOI: 10.1371/journal.pone.0057684
  • NAID: 120005228652
  • Peer Reviewed
• [Journal Article] Novel mutations in Marburg virus glycoprotein associated with viral evasion from antibody mediated immune pressure. (2013)
  • Author(s): Kajihara, M., et al.
  • Journal Title: Journal of general virology Volume: 94 Issue: 4 Pages: 876-883
  • DOI: 10.1099/vir.0.049114-0
  • Peer Reviewed
• [Journal Article] Molecular mechanisms underlying oseltamivir resistance mediated by an I117V substitution in the NA of H5N1 avian influenza viruses (2013)
  • Author(s): Takano R, Kiso M, Igarashi M, Le QM, Sekijima M, Ito K, Takada A, Kawaoka Y
  • Journal Title: J Infect Dis Volume: 207 Issue: 1 Pages: 89-97
  • DOI: 10.1093/infdis/jis633
  • Peer Reviewed
• [Journal Article] An H5N1 highly pathogenic avian influenza virus that invaded Japan through waterfowl migration (2013)
  • Author(s): Kajihara M, Matsuno K, Simulundu E, Muramatsu M, Noyori O, Manzoor R, Nakayama E, Igarashi M, Tomabechi D, Yoshida R, Okamatsu M, Sakoda Y, Ito K, Kida H, Takada A
  • Journal Title: Jpn J Vet Res Volume: 59 Pages: 89-100
  • NAID: 120003354967
  • URL: http://hdl.handle.net/2115/47149
  • Peer Reviewed
• [Journal Article] Differential potential for envelope gycoprotein-mediated steric shielding of host cell surface proteins among filoviruses (2013)
  • Author(s): Noyori Osamu
  • Journal Title: Virology Volume: 446 Issue: 1-2 Pages: 152-161
  • DOI: 10.1016/j.virol.2013.07.029
  • Peer Reviewed
• [Journal Article] Cysteine Residues in the Major Capsid Protein, Vp1, of the JC Virus Are Important for Protein Stability and Oligomer Formation (2013)
  • Author(s): Kobayashi S, Suzuki T, Igarashi M, Orba Y, Ohtake N, Nagakawa K, Niikura K, Kimura T, Kasamatsu H, Sawa H
  • Journal Title: PLoS One Volume: 8(10) Issue: 10 Pages: e76668-e76668
  • DOI: 10.1371/journal.pone.0076668
  • NAID: 120005350093
  • Peer Reviewed
• [Journal Article] High prevalence of spotted fever group rickettsiae in Amblyomma variegatum from Uganda and their identification using sizes of intergenic spacers (2013)
  • Author(s): Nakao R, Qiu Y, Igarashi M, Magona JW, Zhou L, Ito K, Sugimoto C
  • Journal Title: Ticks and Tick-Borne Disease Volume: 4(6) Issue: 6 Pages: 506-512
  • DOI: 10.1016/j.ttbdis.2013.07.001
  • Peer Reviewed
• [Journal Article] Antiviral activity of stachyflin on influenza a viruses of different hemagglutinin subtypes (2013)
  • Author(s): Motohashi Y, Igarashi M, Okamatsu M, Noshi T, Sakoda Y, Yamamoto N, Ito K, Yoshida R, Kida H.
  • Journal Title: Virol J Volume: 10 Pages: 118-118
  • NAID: 120005323601
  • Peer Reviewed
• [Journal Article] Protective efficacy of neutralizing monoclonal antibodies in a nonhumar primate model of ebola hemorrhagic Fever (2012)
  • Author(s): Marzi A, Yoshida R, Miyamoto H, Ishijima M, Suzuki Y, Higuchi M, Matsuyama Y, Igarashi M, Nakayama E, Kuroda M, Saijo M, Feldmann F, Brining D, Feldmann H, Takada A
  • Journal Title: PLoS One Volume: 7(4) Issue: 4 Pages: e36192-e36192
  • DOI: 10.1371/journal.pone.0036192
  • Peer Reviewed
• [Journal Article] Tobacco calmodulin-like protein provides secondary defense by binding to and directing degradation of virus RNA silencing suppressors (2012)
  • Author(s): Nakahara KS, Masuta C, Yamada S, Shimura H, Kashihara Y, Wada TS, Meguro A, Goto K, Tadamura K, Sueda K, Sekiguchi T, Shao J, Itchoda N, Matsumura T, Igarashi M, Ito K, Carthew RW, Uyeda I
  • Journal Title: Proc Natl Acad Sci U S A Volume: 109 Issue: 25 Pages: 10113-10118
  • DOI: 10.1073/pnas.1201628109
  • Peer Reviewed
• [Journal Article] Serological evidence of ebola virus infection in indonesian orangutans (2012)
  • Author(s): Nidom CA, Nakayama E, Nidom RV, Alamudi MY, Daulay S, Dharmayanti IN, Dachlan YP, Amin M, Igarashi M, Miyamoto H, Yoshida R, Takada A
  • Journal Title: PLoS One Volume: 7 Issue: 7 Pages: e40740-e40740
  • DOI: 10.1371/journal.pone.0040740
  • Peer Reviewed
• [Journal Article] The Conserved Region in the PrM Protein Is a Critical Determinant in the Assembly of Flavivirus Particles (2012)
  • Author(s): Yoshii K, Igarashi M, Ichii O, Yokozawa K, Ito K, Kariwa H, Takashima I
  • Journal Title: Journal of General Virology Volume: 93 Issue: 1 Pages: 27-38
  • DOI: 10.1099/vir.0.035964-0
  • Peer Reviewed
• [Journal Article] Virus capsid coating of gold nanoparticles via cysteine-Au interactions and their effective cellular uptakes (2012)
  • Author(s): Keita Nagakawa, Keinchi Niikura, Tadaki Suzuki, Yasutaka Matsuo, Manabu Igarashi, Hirofumi Sawa, Kuniharu Ijiro
  • Journal Title: Chemistry Letters Volume: 41 Issue: 1 Pages: 113-115
  • DOI: 10.1246/cl.2012.113
  • NAID: 10030222850
  • Peer Reviewed
• [Journal Article] Gnarled-trunk evolutionary model of influenza A virus hemagglutinin (2011)
  • Author(s): Ito K, Igarashi M, Miyazaki Y, Murakami T, Iida S, Kida H, Takada A
  • Journal Title: PLoS ONE Volume: 6(10) Issue: 10 Pages: e25953-e25953
  • DOI: 10.1371/journal.pone.0025953
  • NAID: 120005476103
  • Peer Reviewed
• [Journal Article] An H5N1 highly pathogenic avian influenza virus that invaded Japan through waterfowl migration. (2011)
  • Author(s): Kajihara M, Matsuno K, Simulundu E, Muramatsu M, Noyori O, Manzoor R, Nakayama E, Igarashi M, Tomabechi D, Yoshida R, Okamatsu M, Sakoda Y, Ito K, Kida H, Takada A
  • Journal Title: Jpn J Vet Res. Volume: 59 Pages: 89-100
  • NAID: 120003354967
  • Peer Reviewed
• [Journal Article] Single amino acid residue in the A2 domain of major histocompatibility complex class I is involved in the efficiency of equine herpesvirus-1 entry. (2011)
  • Author(s): Sasaki M, Kim E, Igarashi M, Ito K, Hasebe R, Fukushi H, Sawa H, Kimura T
  • Journal Title: J Biol Chem. Volume: 286 Issue: 45 Pages: 39370-39378
  • DOI: 10.1074/jbc.m111.251751
  • NAID: 120005652751
  • Peer Reviewed
• [Journal Article] Prediction of the antigenic changes of the pandemic (H1N1) 2009 influenza virus hemagglutinin (2011)
  • Author(s): Igarashi M, Ito K, Yoshida R, Tomabechi D, Kida H, Takada A
  • Journal Title: Influenza and other respiratory viruses Volume: 5 (supple. 1) Pages: 402-404
  • Peer Reviewed
• [Presentation] インフルエンザウイルス蛋白質の計算科学的解析 (2014)
  • Author(s): 五十嵐学
  • Organizer: 日本薬学会第134年会
  • Place of Presentation: 熊本大学（熊本県熊本市）
  • Invited
• [Presentation] Resampling of Large Nucleotide Sequence Datasets of Viruses with Closest-Neighbor Trimming Method (2013)
  • Author(s): Yonezawa K, Igarashi M, Ito K
  • Organizer: The 21st Annual Conference of the Society for Molecular Biology and Evolution
  • Place of Presentation: Hyatt Regency Chicago（Chicago, USA）
• [Presentation] De novo designed molecule to develop structure-based vaccine against Anthrax (2013)
  • Author(s): 大西なおみ、武藤芽未、藤倉大輔、五十嵐学、東秀明
  • Organizer: 第60回毒素シンポジウム
  • Place of Presentation: 楓香荘（兵庫県宍粟市）
• [Presentation] 豚コレラウイルスの豚に対する病原性に関与するウイルス表面糖蛋白E2の機能解析 (2013)
  • Author(s): 田村友和、迫田義博、五十嵐学、Nicolas R、伊藤公人、岡松正敏、喜田宏
  • Organizer: 第47回日本ウイルス学会北海道支部会夏季シンポジウム
  • Place of Presentation: ホテル北の湯（北海道奈井江町）
• [Presentation] 新規抗炭疽ワクチンの開発に向けた人工設計タンパク質の作出 (2013)
  • Author(s): 武藤芽未、大西なおみ、藤倉大輔、五十嵐学、東秀明
  • Organizer: 第7回細菌学若手コロッセウム
  • Place of Presentation: 広島エアポートホテル（広島県三原市）
• [Presentation] novo designed molecule to develop structure-based vaccine against Anthrax (2013)
  • Author(s): 大西なおみ、武藤芽未、藤倉大輔、五十嵐学、東秀明
  • Organizer: 第12回あわじしま感染症・免疫フォーラム
  • Place of Presentation: 淡路夢舞台国際会議場（兵庫県淡路市）
• [Presentation] ダニ媒介性フラビウイルスによる中枢神経系病態におけるNS5蛋白の影響の解析 (2013)
  • Author(s): 好井健太朗、寸田祐嗣、五十嵐学、横澤香菜、境瑞紀、苅和宏明、Michael Holbrook、高島郁夫
  • Organizer: 第156回日本獣医学会学術集会
  • Place of Presentation: 岐阜大学（岐阜県岐阜市）
• [Presentation] ダニ媒介性フラビウイルスによる中枢神経系病態に関わるウイルス因子の同定 (2013)
  • Author(s): 好井健太朗、寸田祐嗣、五十嵐学、横澤香菜、境瑞紀、苅和宏明、Michael Holbrook
  • 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（兵庫県神戸市）
• [Presentation] 第一原理計算を用いたインフルエンザウイルス表面糖タンパク質とマルチターゲット医薬リード天然物との高精度相互作用解析 (2013)
  • Author(s): 石坪江梨花、Kirshner Karl N、五十嵐学、Sriwilaijaroen Nongluk、鈴木康夫、常盤広明
  • 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（兵庫県神戸市）
• [Presentation] 計算科学的手法を用いたインフルエンザウイルスヘマグルチニンと亜型間交差反応性抗体との分子間相互作用の解析 (2013)
  • Author(s): 五十嵐学、吉田玲子、関嶋政和、常盤広明、喜田宏、伊藤公人、高田礼人
  • 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（兵庫県神戸市）
• [Presentation] 近隣結合法による塩基配列データセットのリサンプリングとその性能評価 (2013)
  • Author(s): 米澤弘毅、五十嵐学、伊藤公人
  • Organizer: 人工知能学会 第88回 人工知能基本問題研究会
  • Place of Presentation: 石垣市民会館（沖縄県石垣市）
• [Presentation] 近隣剪定法によるウイルス遺伝子配列のリサンプリング (2013)
  • Author(s): 米澤弘毅、五十嵐学、伊藤公人
  • Organizer: 第7回日本ゲノム微生物学会年会
  • Place of Presentation: 長浜バイオ大学（滋賀県長浜市）
• [Presentation] 炭疽菌毒素の分子立体構造情報に基づいたヒト炭疽予防法の開発 (2013)
  • Author(s): 大西なおみ、武藤芽未、五十嵐学、藤倉大輔、東秀明
  • Organizer: 第86回日本細菌学会総会
  • Place of Presentation: 幕張メッセ（千葉県千葉市）
• [Presentation] 近隣剪定法：進化系統樹を利用した配列リサンプリングアルゴリズム (2012)
  • Author(s): 米澤弘毅、五十嵐学、伊藤公人
  • Organizer: 第29回バイオ情報学研究発表会
  • Place of Presentation: 沖縄科学技術大学院大学メインキャンパス（沖縄県）
• [Presentation] 近隣剪定法によるウイルス遺伝子配列のリサンプリング (2012)
  • Author(s): 米澤弘毅、五十嵐学、高田礼人、伊藤公人
  • Organizer: 第60回日本ウイルス学術集会
  • Place of Presentation: グランキューブ大阪（大阪府大阪市）
• [Presentation] フィロウイルス糖蛋白質による宿主細胞表面分子の立体的遮蔽現象の解析 (2012)
  • Author(s): 野依 修、松野啓太、梶原将大、中山絵里、五十嵐学、磯田典和、吉田玲子、高田礼人
  • Organizer: 第60回日本ウイルス学術集会
  • Place of Presentation: グランキューブ大阪（大阪府大阪市）
• [Presentation] Feldmann Heinz、高田礼人：アカゲザルモデルを用いたエボラ出血熱に対する中和モノクローナル抗体の防御効果 (2012)
  • Author(s): 吉田 玲子、Marzi Andrea、宮本洋子、石島麻理、鈴木 定彦、五十嵐学、中山絵里、黒田 誠、Feldmann Heinz、高田礼人
  • Organizer: 第60回日本ウイルス学術集会
  • Place of Presentation: グランキューブ大阪（大阪府大阪市）
• [Presentation] H3N2インフルエンザウイルスHAへの糖鎖付加と周辺アミノ酸残基にかかる選択圧の経時的変化 (2012)
  • Author(s): 五十嵐学、中尾 亮、喜田 宏、高田礼人、伊藤公人
  • Organizer: 第60回日本ウイルス学術集会
  • Place of Presentation: グランキューブ大阪（大阪府大阪市）
• [Presentation] 簡便なリケッチア種の遺伝子鑑別に向けた新しい試み (2012)
  • Author(s): 中尾 亮、邱 永晋、五十嵐学、Joseph W. Magona、周 麗華、伊藤公人、杉本千尋
  • Organizer: 第5回日本リケッチア症臨床研究会・第19回リケッチア研究会 合同研究発表会
  • Place of Presentation: 滋 賀県立県民交流センター・ピアザ淡海（滋賀県大津市）
• [Presentation] Characterization of Amino Acid Substitutions on Influenza Virus Surface Proteins: A Computational Structural Biology Research (2012)
  • Author(s): 五十嵐学
  • Organizer: 第35回分子生物学会年会
  • Place of Presentation: 福岡国際会議場・マリンメッセ福岡（福岡県福岡市）
  • Invited
• [Presentation] Gnarled-Trunk Evolutionary Model of Influenza A Virus Hemagglutinin (2011)
  • Author(s): Ito K, Igarashi M, Miyazaki Y, Murakami T, Iida S, Kida H, Takada A
  • Organizer: International Union of Microbiological Societies 2011 congress
  • Place of Presentation: 札幌コンベンションセンター（札幌市）
• [Presentation] Enzyme-linked Immunosorbent Assay for the Detection of Filovirus Specie-Specific Antibodies (2011)
  • Author(s): Nakayama E, Yokoyama A, Miyamoto H, Igarashi M, Kishida N, Matsuno K, Marzi A, Feldmann H, Ito K, Saijo M, Takada A
  • Organizer: International Union of Microbiological Societies 2011 congress
  • Place of Presentation: 札幌コンベンションセンター（札幌市）
• [Presentation] An Rgs-CAM-Mediated Countermeasure for RNAi-Based Antiviral Immunity in Tobacco (2011)
  • Author(s): Nakahara K, Masuta C, Yamada S, Shimura H, Wada T, Meguro A, Sueda K, Goto K, Igarashi M, Carthew R, Uyeda I:
  • Organizer: International Union of Microbiological Societies 2011 congress
  • Place of Presentation: 札幌コンベンションセンター（札幌市）
• [Presentation] A Highly Pathogenic Avian Influenza Virus (H5N1) that Invaded Japan through Waterfowl Migration (2011)
  • Author(s): Kajihara M, Matsuno K, Simulundu E, Muramatsu M, Noyori O, Manzoor R, Igarashi M, Okamatsu M, Sakoda Y, Kida H, Takada A
  • Organizer: International Union of Microbiological Societies 2011 congress
  • Place of Presentation: 札幌コンベンションセンター（札幌市）
• [Presentation] Characterization of Monoclonal Antibodies against the 2009 Pandemic H1N1 Influenza Virus Hemagglutinin (2011)
  • Author(s): Yoshida R, Tomabechi D, Igarashi M, Miyamoto H, Yokoyama A, Kase T, Kida H, Takada A
  • Organizer: International Union of Microbiological Societies 2011 congress
  • Place of Presentation: 札幌コンベンションセンター（札幌市）
• [Presentation] Cys80 of JC Virus Capsid Protein, VP1 Is Essential for Pentamer Formation (2011)
  • Author(s): Kobayashi S, Suzuki T, Igarashi M, Ohtake N, Nagakawa K, Niikura K, Kimura T, Kasamatsu H, Sawa H
  • Organizer: International Union of Microbiological Societies 2011 congress
  • Place of Presentation: 札幌コンベンションセンター（札幌市）
• [Presentation] Single Amino Acid Residue in Equine Major Histocompatibility Complex Class I Is Critical for Its Function as An Equine Herpesvirus-1 Receptor (2011)
  • Author(s): Sasaki M, Igarashi M, Sawa H, Hasebe R, Fukushi H, Kimura T
  • Organizer: International Union of Microbiological Societies 2011 congress
  • Place of Presentation: 札幌コンベンションセンター（札幌市）
• [Presentation] Dynamics of Sequence Variation in Antigenic Domains and Glycosylation Sites of Hemagglutinin of Human H3N2 Influenza Viruses (2011)
  • Author(s): Igarashi M, Takada A, Kida H, Ito K
  • Organizer: International Union of Microbiological Societies 2011 congress
  • Place of Presentation: 札幌コンベンションセンター（札幌市）
• [Presentation] An H5N1 highly pathogenic avian influenza virus that invaded Japan through waterfowl migration (2011)
  • Author(s): Kajihara M, Matsuno K, Simulundu E, Muramatsu M, Noyori O, Manzoor R, Nakayama E, Igarashi M, Tomabechi D, Yoshida R, Okamatsu M, Sakoda Y, Ito K, Kida H, Takada A
  • Organizer: The 3rd International Young Researcher Seminar in Zoonosis Control 2011
  • Place of Presentation: 北海道大学（札幌市）
• [Presentation] Reduction of Sampling Bias in Large Datasets by Systematic Trimming of Phylogenetic Trees (2011)
  • Author(s): Yonezawa K, Ueno K, Igarashi M, Ito K
  • Organizer: The 3rd International Young Researcher Seminar in Zoonosis Control 2011
  • Place of Presentation: 北海道大学（札幌市）
• [Presentation] A single amino acid residue in major histocompatibility complex class I is a determinant for its function as an equine herpesvirus-1 receptor (2011)
  • Author(s): Sasaki M, Kim E, Igarashi M, Hasebe R, Sawa H, Ito K, Kimura T
  • Organizer: The 3rd International Young Researcher Seminar in Zoonosis Control 2011
  • Place of Presentation: 北海道大学（札幌市）
• [Remarks]
  • URL: http://www.czc.hokudai.ac.jp/bioinform/members/igarashi/index_j.html
• [Remarks] バイオインフォマティクス部門 メンバーページ
  • URL: http://www.czc.hokudai.ac.jp/bioinform/members/igarashi/index_j.html
• [Remarks]
  • URL: http://www.hokudai.ac.jp/czc/bioinform/members/igarashi/index_j.html