2001 年度実績報告書

ヘマグルチニンの糖鎖認識の多様性とインフルエンザウイルスの宿主間伝播機構

研究課題

研究課題/領域番号	11670301
研究機関	静岡県立大学
研究代表者	鈴木隆静岡県立大学, 薬学部, 助教授 (20240947)
研究分担者	左一八静岡県立大学, 薬学部, 助手 (20260226) 鈴木康夫静岡県立大学, 薬学部, 教授 (00046278)
キーワード	インフルエンザウイルス / シアル酸 / 宿主域 / スルファチド / ヘマグルチニン / N-アセチルノイラミン酸 / N-グリコリルノイラミン酸
研究概要	本研究は、ヘマグルチニン(HA)の多様な糖鎖認識機構を分子レベルで解明することにより、インフルエンザウイルスの感染増殖や異種動物間でのウイルスの伝播におけるヘマグルチニン(HA)の役割を明らかにすることを目的とした。本研究により1)1968年から1979年までのH3型ヒトインフルエンザA型ウイルス株は、非還元末端にN-アセチルノイラミン酸(Neu5Ac)だけでなくN-グリコリルノイラミン酸(Neu5Gc)をα2,6結合した糖鎖にも高い結合性を示すことが判明した。2)ウマ気管支上皮細胞はNeu5Gc 2,3Gal-構造を糖鎖非還元末端に有し、全シアル酸の90%以上がNeu5Gcであることを見出した。さらに、ヒトウイルス株由来のHA遺伝子をウマHA遺伝子の作わりに含有する遺伝子交雑株を用いてウマへの感染増殖性を比較した結果、HAがNeu5Gc 2,3Gal-構造に高い結合性有することが、ウマインフルエンザウイルスの感染性を規定する重要な要因であることを明らかにした。3)Neu5Gc 2,3Gal-構造に高い結合性を有するHA遺伝子交雑株のみが、カモ由来ウイルス株と同様にカモ腸管で増殖することを明らかにした。さらに糖鎖抗体を用いた免疫組織染色法によりHAがNeu5Gc 2,3Gal-構造に高い結合性を有することが、カモへの感染増殖において重要であることを明らかにした。4)スルファチドは、HAのシアロ糖鎖結合部位もしくはその近傍に結合していることを明らかにした。

研究成果
(20件)

すべてその他

すべて文献書誌 (20件)

[文献書誌] Hiroyuki Masuda: "Substitution of amino acid residue in influenza A virus hemagglutinin affects recognition of sialyl-oligosaccharides containing N-glycolylneuraminic acid"FEBS Lett.. 464. 71-74 (1999)
[文献書誌] Chao-Tan Guo: "Gangliosides GM1a on the cell surface is involved in the infection by human rotavirus KUN and MO strains"J.Biochem.. 126. 683-688 (1999)
[文献書誌] Darwyn Kobasa: "Amino acid residures contributing to the substrate specificity of the influenza A virus neuraminidase"J.Virol.. 73. 6743-6751 (1999)
[文献書誌] Kenichi Shikata: "L-selectin and its ligands mediate infiltration of mononuclear cells into kidney interstitium after ureteric obstruction"J.Pathol.. 188. 93-99 (1999)
[文献書誌] Yasuhiro Hosaka: "Binding of influenza type A viruses to group B Streptococcus and haemagglutination by virus-bound bacteria"J.Electron Microsc.. 49. 765-773 (2000)
[文献書誌] Yasuo Suzuki: "Sialic acid species as a determinant of the host range of influenza A viruses"J.Virol.. 74. 11825-11831 (2000)
[文献書誌] Toshihiro Ito: "Recognition of N-glycolylneuraminic acid linked to galactose by the α2,3 linkage is associated with the intestinal replication of influenza A virus in ducks"J.Virol.. 74. 9300-9305 (2000)
[文献書誌] Tetsuya Furuike: "Synthesis and anti-influenza virus activity of novel glycopolymers having triantennary oligosaccharide branches"J.Chem.Soc.Perkin Trans. 1. 3000-3005 (2000)
[文献書誌] Akiko Eguchi: "Identification and characterization of cell lines with a defect in a post-adsorption stage of Sendai virus-mediated membrane fusion"J.Biol.Chem.. 275. 17549-17555 (2000)
[文献書誌] Yuichi Kawai: "Anti-mouse sperm monoclonal antibody, A-1, inhibits sperm capacitation, acrosome reaction and calcium influx into spermatocytes"Biol.Pharm.Bull.. 23. 922-925 (2000)
[文献書誌] Kazuhiko Hayashi: "Inactivation of human type A and B influenza viruses by tea-seed saponins"Biosoi.Biotechnol.Biochem.. 64. 184-186 (2000)
[文献書誌] Kiyoshi Ikeda: "Synthesis of 2-deoxy-2,3-didehydro-N-acetylneuraminic acid analogues modified at the C-4 and C-9 positions and their behaviour towards sialidase from influenza virus and pig liver membrane"Carbohydr.Res.. 330. 31-41 (2001)
[文献書誌] Mark T.Hughes: "Adaptation of Influenza A viruses to cells expressing low levels of sialic acid leads to loss of neuraminidase activity"J.Virol.. 75. 3766-3770 (2001)
[文献書誌] Masafumi Kimura: "Engagement of endogenous ganglioside GM1a induces tyrosine phospholation involved in neuron-like differentiation of PC12"Glycobiol. 11. 335-343 (2001)
[文献書誌] Takashi Suzuki: "Receptor specificities of the human respiroviruses"J.Virol.. 75. 4604-4613 (2001)
[文献書誌] Tadanobu Takahashi: "Duck and human pandemic influenza A viruses retain sialidase activity in low pH conditions"J.Biochem.. 130. 279-283 (2001)
[文献書誌] Chao-Tan Guo: "A Unique Phosphatidylinositol Bearing a Novel Branched-Chain Fatty Acid from Rhodococcus equi Binds to Influenza Virus Hemagglutinin and Inhibits the Infection of Cells"J.Biochem.. 130. 377-384 (2001)
[文献書誌] Takehiko Saito: "Characterization of a human H9N2 influenza virus isolated in Hong Kong"Vaccine. 20. 125-133 (2001)
[文献書誌] Takashi Suzuki: "Inhibition of human parainfluenza virus type 1 neuraminidase by analogs of 2-deoxy-2,3-didehydro-N-acetylneuraminic aicd"Glycoconjugate J.. 18. 331-337 (2001)
[文献書誌] Chao-Tan Guo: "An O-glycoside of sialic acid derivative that inhibits both hemagglutinin and sialidase activities of influenza viruses"Glycobiol. (in press).

2001 年度 実績報告書

ヘマグルチニンの糖鎖認識の多様性とインフルエンザウイルスの宿主間伝播機構

研究代表者

鈴木 隆 静岡県立大学, 薬学部, 助教授 (20240947)

研究成果

[文献書誌] Hiroyuki Masuda: "Substitution of amino acid residue in influenza A virus hemagglutinin affects recognition of sialyl-oligosaccharides containing N-glycolylneuraminic acid"FEBS Lett.. 464. 71-74 (1999)

[文献書誌] Chao-Tan Guo: "Gangliosides GM1a on the cell surface is involved in the infection by human rotavirus KUN and MO strains"J.Biochem.. 126. 683-688 (1999)

[文献書誌] Darwyn Kobasa: "Amino acid residures contributing to the substrate specificity of the influenza A virus neuraminidase"J.Virol.. 73. 6743-6751 (1999)

[文献書誌] Kenichi Shikata: "L-selectin and its ligands mediate infiltration of mononuclear cells into kidney interstitium after ureteric obstruction"J.Pathol.. 188. 93-99 (1999)

[文献書誌] Yasuhiro Hosaka: "Binding of influenza type A viruses to group B Streptococcus and haemagglutination by virus-bound bacteria"J.Electron Microsc.. 49. 765-773 (2000)

[文献書誌] Yasuo Suzuki: "Sialic acid species as a determinant of the host range of influenza A viruses"J.Virol.. 74. 11825-11831 (2000)

[文献書誌] Toshihiro Ito: "Recognition of N-glycolylneuraminic acid linked to galactose by the α2,3 linkage is associated with the intestinal replication of influenza A virus in ducks"J.Virol.. 74. 9300-9305 (2000)

[文献書誌] Tetsuya Furuike: "Synthesis and anti-influenza virus activity of novel glycopolymers having triantennary oligosaccharide branches"J.Chem.Soc.Perkin Trans. 1. 3000-3005 (2000)

[文献書誌] Akiko Eguchi: "Identification and characterization of cell lines with a defect in a post-adsorption stage of Sendai virus-mediated membrane fusion"J.Biol.Chem.. 275. 17549-17555 (2000)

[文献書誌] Yuichi Kawai: "Anti-mouse sperm monoclonal antibody, A-1, inhibits sperm capacitation, acrosome reaction and calcium influx into spermatocytes"Biol.Pharm.Bull.. 23. 922-925 (2000)

[文献書誌] Kazuhiko Hayashi: "Inactivation of human type A and B influenza viruses by tea-seed saponins"Biosoi.Biotechnol.Biochem.. 64. 184-186 (2000)

[文献書誌] Kiyoshi Ikeda: "Synthesis of 2-deoxy-2,3-didehydro-N-acetylneuraminic acid analogues modified at the C-4 and C-9 positions and their behaviour towards sialidase from influenza virus and pig liver membrane"Carbohydr.Res.. 330. 31-41 (2001)

[文献書誌] Mark T.Hughes: "Adaptation of Influenza A viruses to cells expressing low levels of sialic acid leads to loss of neuraminidase activity"J.Virol.. 75. 3766-3770 (2001)

[文献書誌] Masafumi Kimura: "Engagement of endogenous ganglioside GM1a induces tyrosine phospholation involved in neuron-like differentiation of PC12"Glycobiol. 11. 335-343 (2001)

[文献書誌] Takashi Suzuki: "Receptor specificities of the human respiroviruses"J.Virol.. 75. 4604-4613 (2001)

[文献書誌] Tadanobu Takahashi: "Duck and human pandemic influenza A viruses retain sialidase activity in low pH conditions"J.Biochem.. 130. 279-283 (2001)

[文献書誌] Chao-Tan Guo: "A Unique Phosphatidylinositol Bearing a Novel Branched-Chain Fatty Acid from Rhodococcus equi Binds to Influenza Virus Hemagglutinin and Inhibits the Infection of Cells"J.Biochem.. 130. 377-384 (2001)

[文献書誌] Takehiko Saito: "Characterization of a human H9N2 influenza virus isolated in Hong Kong"Vaccine. 20. 125-133 (2001)

[文献書誌] Takashi Suzuki: "Inhibition of human parainfluenza virus type 1 neuraminidase by analogs of 2-deoxy-2,3-didehydro-N-acetylneuraminic aicd"Glycoconjugate J.. 18. 331-337 (2001)

[文献書誌] Chao-Tan Guo: "An O-glycoside of sialic acid derivative that inhibits both hemagglutinin and sialidase activities of influenza viruses"Glycobiol. (in press).

2001 年度実績報告書

鈴木隆静岡県立大学, 薬学部, 助教授 (20240947)