Computational analysis of a conformational epitope of a broadly neutralizing antibody in influenza A virus hemagglutinin
Project/Area Number |
25450417
|
Research Category |
Grant-in-Aid for Scientific Research (C)
|
Allocation Type | Multi-year Fund |
Section | 一般 |
Research Field |
Veterinary medical 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, 准教授 (10374240)
|
Co-Investigator(Renkei-kenkyūsha) |
TAKADA AYATO 北海道大学, 人獣共通感染症リサーチセンター, 教授 (10292062)
|
Project Period (FY) |
2013-04-01 – 2017-03-31
|
Project Status |
Completed (Fiscal Year 2016)
|
Budget Amount *help |
¥5,200,000 (Direct Cost: ¥4,000,000、Indirect Cost: ¥1,200,000)
Fiscal Year 2015: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000)
Fiscal Year 2014: ¥780,000 (Direct Cost: ¥600,000、Indirect Cost: ¥180,000)
Fiscal Year 2013: ¥3,510,000 (Direct Cost: ¥2,700,000、Indirect Cost: ¥810,000)
|
Keywords | インフルエンザ / ウイルス / 抗体 / 計算科学 / 分子動力学 / 分子モデリング / 分子動力学計算 / 分子間相互作用 / ホモロジーモデリング |
Outline of Final Research Achievements |
The HA of influenza A viruses is classified into 16 subtypes (H1-H16). We have previously reported a cross-reactive antibody, designated S139/1, which neutralizes H1, H2, H3, H13, and H16 subtypes. In this study, we characterized the S139/1 recognition sites on different HAs by computational methods such as molecular modeling and dynamics simulations. We investigated the contribution of individual residues on each HA to the interaction with S139/1, and found that amino acids at 10 positions on HA strongly contributed to S139/1 binding as for the strains neutralized by S139/1. Analysis of hydrogen bond interactions emphasized that the residues at positions 156, 158 and 193 were the most important for S139/1 binding. Indeed, amino acid substitutions at these three positions were experimentally observed in the mutant viruses escaping from neutralization by S139/1. Thus, our computational methods identified the amino acid residues critical for the cross-neutralizing activity of S139/1.
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Report
(5 results)
Research Products
(51 results)
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[Journal Article] Genetic predisposition to acquire a polybasic cleavage site for highly pathogenic avian influenza virus hemagglutinin2017
Author(s)
Nao N, Yamagishi J, Miyamoto H, Igarashi M, Manzoor R, Ohnuma A, Tsuda Y, Furuyama W, Shigeno A, Kajihara M, Kishida N, Yoshida R, Takada A
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Journal Title
MBio
Volume: 8
Issue: 1
Pages: 1-15
DOI
NAID
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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[Journal Article] Fcγ-receptor IIa-mediated Src signaling pathway is essential for the antibody-dependent enhancement of Ebola virus infection2016
Author(s)
Furuyama W, Marzi A, Carmody AB, Maruyama J, Kuroda M, Miyamoto H, Nanbo A, Manzoor R, Yoshida R, Igarashi M, Feldmann H, Takada A
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Journal Title
PLoS Pathog.
Volume: 12
Issue: 12
Pages: e1006139-e1006139
DOI
NAID
Related Report
Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
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[Journal Article] Discovery of an antibody for pan-ebolavirus therapy2016
Author(s)
Furuyama D, Marzi A, Nanbo A, Haddock E, Maruyama J, Miyamoto H, Igarashi M, Yoshida R, Dr. Noyori O, Feldmann H, Takada A
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Journal Title
Sci Rep
Volume: 6
Issue: 1
Pages: 20514-20514
DOI
NAID
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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[Journal Article] A Single Amino Acid in the M1 Protein Responsible for the Different Pathogenic Potentials of H5N1 Highly Pathogenic Avian Influenza Virus Strains2015
Author(s)
Nao N, Kajihara M, Manzoor R, Maruyama J, Yoshida R, Muramatsu M, Miyamoto H, Igarashi M, Eguchi N, Sato M, Kondoh T, Okamatsu M, Sakoda Y, Kida H, Takada A
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Journal Title
PLoS One
Volume: 10(9)
Issue: 9
Pages: e0137989-e0137989
DOI
NAID
Related Report
Peer Reviewed / Open Access
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[Journal Article] Emergence of H7N9 Influenza A Virus Resistant to Neuraminidase Inhibitors in Nonhuman Primates2015
Author(s)
Itoh Y, Shichinohe S, Nakayama M, Igarashi M, Ishii A, Ishigaki H, Ishida H, Kitagawa N, Sasamura T, Shiohara M, Doi M, Tsuchiya H, Nakamura S, Okamatsu M, Sakoda Y, Kida H, Ogasawara K
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Journal Title
Antimicrob Agents Chemother
Volume: 59(8)
Issue: 8
Pages: 4962-4973
DOI
Related Report
Peer Reviewed / Open Access
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[Journal Article] The zoonotic potential of avian influenza viruses isolated from wild waterfowl in Zambia2014
Author(s)
Simulundu E, Nao N, Yabe J, Muto NA, Sithebe T, Sawa H, Manzoor R, Kajihara M, Muramatsu M, Ishii A, Ogawa H, Mweene AS, Takada A
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Journal Title
Arch. Virol.
Volume: 159
Issue: 6
Pages: 2633-2640
DOI
NAID
Related Report
Peer Reviewed / Open Access
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[Journal Article] Cysteine Residues in the Major Capsid Protein, Vp1, of the JC Virus Are Important for Protein Stability and Oligomer Formation2013
Author(s)
Kobayashi S, Suzuki T, Igarashi M, Orba Y, Ohtake N, Nagakawa K, Niikura K, Kimura T, Kasamatsu H, Sawa H
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Journal Title
PLoS One
Volume: 8(10)
Issue: 10
Pages: e76668-e76668
DOI
NAID
Related Report
Peer Reviewed
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[Presentation] Generation of a cross-neutralizing monoclonal antibody against all known ebolavirus species2016
Author(s)
Furuyama W, Marzi A, Nanbo A, Haddock E, Maruyama J, Miyamoto H, Igarashi M, Yoshida R, Noyori O, Feldmann H, Takada A
Organizer
第64回日本ウイルス学会学術集会
Place of Presentation
北海道札幌市、札幌コンベンションセンター
Year and Date
2016-10-23
Related Report
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[Presentation] Genetic Predisposition to Acquire a Polybasic Cleavage Site for Highly Pathogenic Avian Influenza Virus Hemagglutinin2016
Author(s)
Nao N, Yamagishi J, Miyamoto H, Igarashi M, Manzoor R, Ohnuma A, Tsuda Y, Furuyama W, Kajihara M, Yoshida R, Takada A
Organizer
第64回日本ウイルス学会学術集会
Place of Presentation
北海道札幌市、札幌コンベンションセンター
Year and Date
2016-10-23
Related Report
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[Presentation] Computational analysis of a conformational epitope of a broadly neutralizing antibody in influenza A virus hemagglutinin2016
Author(s)
Igarashi M, Sekijima M, Yasuo N, Abe T, Yoshida R, Tokiwa H, Watabe T, Hirokawa T, Takada A
Organizer
Options IX for the Control of Influenza
Place of Presentation
Chicago, Illinois, USA
Year and Date
2016-08-24
Related Report
Int'l Joint Research
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[Presentation] Molecular analysis on receptor-binding of H5 influenza viruses to fucosylated α2,3 sialosides2016
Author(s)
Hiono T, Okamatsu M, Igarashi M, McBride R, de Vries RP, Peng W, Paulson J, Sakoda Y, Kida H
Organizer
Options IX for the Control of Influenza
Place of Presentation
Chicago, Illinois, USA
Year and Date
2016-08-24
Related Report
Int'l Joint Research
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[Presentation] A genetic basis for the acquisition of basic amino acid residues at the cleavage site of influenza virus hemagglutinin2016
Author(s)
Nao N, Yamagishi J, Miyamoto H, Ohnuma A, Furuyama W, Tsuda Y, Manzoor R, Yoshida R, Igarashi M, Takada A
Organizer
Options IX for the Control of Influenza
Place of Presentation
Chicago, Illinois, USA
Year and Date
2016-08-24
Related Report
Int'l Joint Research
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