1998 Fiscal Year Annual Research Report

アジアにおける新変異インフルエンザウイルスの出現機構の解明とその制御

Research Project

Project/Area Number	09044328
Research Institution	UNIVERSITY OF SHIZUOKA
Principal Investigator	鈴木康夫静岡県立大学, 薬学部, 教授 (00046278)
Co-Investigator(Kenkyū-buntansha)	ショートリッジケネディホンコン大学, 教授河岡義裕ウイスコンシン大学, 獣医学部, 教授
Keywords	インフルエンザウイルス / インフルエンザ / アジア / シアル酸 / 糖鎖 / ヘマグルチニン / ノイラミニダーゼ / 宿主域変異
Research Abstract	本年度の研究で以下の結果が明らかとなった。 1) 宿主の受容体シアロ糖鎖は、動物からヒトへの伝播を可能にする受容体認識特異性の異なる新型インフルエンザウイルスを発生させるウイルス進化上の選択圧力となる。 2) ブタ気道上皮細胞はトリおよびヒトインフルエンザウイルスの両者を結合できる受容体シアロ糖鎖(ヒトに対してはNeu5Ac2-6Gal、トリに対してはNeu5Ac2-3Gal)を持っている。この結果は、アジアにおけるブタがヒトおよびトリインフルエンザウイルスを自然界において混合させる容器となっていることが判明した。これにより、アジアにおける新型のインフルエンザウイルス発生の機構が明らかとなった。 3) 宿主域依存性の選択は宿主細胞の受容体レベルおよび宿主の抗体圧力により起こる。この際、アミノ酸の点置換を伴う遺伝子の変異がおこる。すなわち、レセプター結合ポケット内Leu226→Glnの変異は、Neu5Ac2-6Gal→Neu5Ac2-3Galへの変異を伴い、抗原決定領域にあるSer205→Tyrの変異はNeu5Ac2-3Gal→Neu5Ac2-6Galへの変異を起こす。上記の結果は、本研究の目的が概ね達成され、さらに付加的な研究結果も得られたことを示している。

Research Products

(28 results)

All Other

All Publications (28 results)

[Publications] Ito,T.: "Differences of sialic acid-galactose linkages in the chicken egg smnion allantois influence human influenza virus receptor specificity and variant selection." J.Virol.71(4). 3357-3362 (1997)
[Publications] Ito,T.: "Receptor specificity of influenza A viruses correlates with the hemagglutination of erythrocytes from different animal species." Virology. 222. 493-499 (1997)
[Publications] Suzuki,T: "Swine Influenza virus strains recognize sialylsugar chains containing the molecular species of sialic acid predominantly present in the swine tracheal epitherium." FEBS Lett.404. 192-196 (1997)
[Publications] Miyamoto,D.: "Establishment of a monoclonal antibody directed to Gb3Cer/CD77: A useful immunochemical reagent for a differentiation marker in Burkitt lymphomas and germinal center B cells." Glycoconjugate J.14. 379-388 (1997)
[Publications] Higashi,H: "Intervantion in endotoxin shock by sulfatide (I3SO3-GalCer) with a concominant reduction in tumor necrosis factor alpha production." Infection and Immunity. 65(4). 1223-1227 (1997)
[Publications] Kaneda,K.: "Glycosphingolipid-binding protein of Borrelia burgdorfewri Sensu Lato." Infection and Immunity. 65(8). 3180-3185 (1997)
[Publications] Ding,Z.: "A sulfatide receptor distinct from L-selectin is involved in lymphocyte activation" FEBS Letters. 418. 310-314 (1997)
[Publications] Tezuka,M.: "茶葉カテキン類のインフルエンザウイルスに対する不活化作用" Jpn J. Toxicol.and Environmental Health(衛生化学). 43(5). 311-315 (1997)
[Publications] Ikami,T.: "Synthesis and biological activity of the novel sulfated and phosphorylated bivalent β-D-galactopyranosides containing fatty acid-alkyl residues." Chem.Pharm.Bull.45,(10). 1726-1728 (1998)
[Publications] Suziki,M: "Platelet disaggregation by PAF antagonists and hydrolysis of exogenous PAF by ecto-type PAF acetylhydrolase." Am.J.Physiol.274(Cell Physiol,43). C47-C57 (1998)
[Publications] Ikami,T.: "Synthetic studies on selectin ligands/inhibitors: Synthesis and inhibitory activity of 2-O-fucosyl sulfatides containing 2-branched fatty-alkyl residues in place of ceramide." J.Carbohydr.Chem. 17(3). 453-470 (1998)
[Publications] Sato,K.: "Specificity of the N1 and N2 sialidase subtypes from human-influenza A virus for naturally occurring and synthetic gangliosides." Glycobiology. 8. 527-532 (1998)
[Publications] Kaneda,K: "Infectivity and arthritis-induction of Borrelia japonica on SCID mice and immune competent mice: possible role of galactosylceramide binding activity on initiation of infection" Microbiol.Immunol.42(3). 171-175 (1998)
[Publications] Kamitakahara,H.: "Lysoganglioside/poly-L-glutamic acid conjugate as picomolar inhibitor of influenza hemagglutinin" Angew.Chem,Int.Ed.Engl.110(11). 1524-1528 (1998)
[Publications] Ryan-Poirier,K.,: "Changes in H3 influenza A virus receptor specificity during replication in humans." Virus Res.56. 169-176 (1998)
[Publications] Miyamoto,D.,: "Thuaplicin-copper chelates inhibit replication of human influenza viruses" Antiviral Res.39. 89-100 (1998)
[Publications] Hosaka,Y.: "Binding of influenza and paramyxoviruses to group B Streptococcus with the terminal sialyl-galactose linkage. ,169-174(1998)." J.Electron Microscopy. 47(2). 169-174 (1998)
[Publications] Ikeda,K.: "Chemoenzymaticsynthesis of an N-acetylneuraminic acid analogue having a carbamoylmethylgroup at C-4 as an inhibitor of sialidase from influenza virus.312,183-189(1998)." Carbohydrate Res.312. 183-189 (1998)
[Publications] Tsuchida,A.: "Simple synthesis of sialyllactose-carrying polystylene and its binding with influenza virus." Glycoconjugate J.No.11(in press). (1999)
[Publications] Shikata,K.: "L-selectin and its ligands mediate the infiltration of mononuclear cells into kidney interstitium after ureteral obstruction." Am.J.Pathol.(in press). (1999)
[Publications] 鈴木康夫: "インフルエンザウイルスレセプター破壊酵素、ノイラミニダーゼ(NA)のウイルス出芽における役割" 日本臨床、特集:インフルエンザウイルス感染の分子病理学. 特集号. 162-167 (1997)
[Publications] 鈴木康夫: "インフルエンザウイルスの宿主域とレセプター特異性" 日本臨床、特集:インフルエンザウイルス感染の分子病理学. 特集号. 142-149 (1997)
[Publications] 鈴木康夫: "インフルエンザウイルスの感染と糖鎖" バイオインダストリー. 55(4). 37-38 (1997)
[Publications] 鈴木康夫: "セレクチンのリガンド" 炎症と免疫. 5(5). 494-503 (1997)
[Publications] 鈴木康夫: "Ligands for Selectins" 動脈硬化. 25(3). 105-112 (1997)
[Publications] 鈴木康夫: "インフルエンザウイルスの宿主域変異の分子機構" ファルマシア. 34(6). 678-683 (1998)
[Publications] 鈴木康夫: "インフルエンザウイルスと糖鎖認識" 蛋白質核酸酵素、特集「糖鎖生物学」. 43(12). 1112-1118 (1998)
[Publications] 鈴木康夫(共著): "感染症実験講座" 丸善, 367 (1998)

1998 Fiscal Year Annual Research Report

アジアにおける新変異インフルエンザウイルスの出現機構の解明とその制御

Principal Investigator

鈴木 康夫 静岡県立大学, 薬学部, 教授 (00046278)

Research Products

[Publications] Ito,T.: "Differences of sialic acid-galactose linkages in the chicken egg smnion allantois influence human influenza virus receptor specificity and variant selection." J.Virol.71(4). 3357-3362 (1997)

[Publications] Ito,T.: "Receptor specificity of influenza A viruses correlates with the hemagglutination of erythrocytes from different animal species." Virology. 222. 493-499 (1997)

[Publications] Suzuki,T: "Swine Influenza virus strains recognize sialylsugar chains containing the molecular species of sialic acid predominantly present in the swine tracheal epitherium." FEBS Lett.404. 192-196 (1997)

[Publications] Miyamoto,D.: "Establishment of a monoclonal antibody directed to Gb3Cer/CD77: A useful immunochemical reagent for a differentiation marker in Burkitt lymphomas and germinal center B cells." Glycoconjugate J.14. 379-388 (1997)

[Publications] Higashi,H: "Intervantion in endotoxin shock by sulfatide (I3SO3-GalCer) with a concominant reduction in tumor necrosis factor alpha production." Infection and Immunity. 65(4). 1223-1227 (1997)

[Publications] Kaneda,K.: "Glycosphingolipid-binding protein of Borrelia burgdorfewri Sensu Lato." Infection and Immunity. 65(8). 3180-3185 (1997)

[Publications] Ding,Z.: "A sulfatide receptor distinct from L-selectin is involved in lymphocyte activation" FEBS Letters. 418. 310-314 (1997)

[Publications] Tezuka,M.: "茶葉カテキン類のインフルエンザウイルスに対する不活化作用" Jpn J. Toxicol.and Environmental Health(衛生化学). 43(5). 311-315 (1997)

[Publications] Ikami,T.: "Synthesis and biological activity of the novel sulfated and phosphorylated bivalent β-D-galactopyranosides containing fatty acid-alkyl residues." Chem.Pharm.Bull.45,(10). 1726-1728 (1998)

[Publications] Suziki,M: "Platelet disaggregation by PAF antagonists and hydrolysis of exogenous PAF by ecto-type PAF acetylhydrolase." Am.J.Physiol.274(Cell Physiol,43). C47-C57 (1998)

[Publications] Ikami,T.: "Synthetic studies on selectin ligands/inhibitors: Synthesis and inhibitory activity of 2-O-fucosyl sulfatides containing 2-branched fatty-alkyl residues in place of ceramide." J.Carbohydr.Chem. 17(3). 453-470 (1998)

[Publications] Sato,K.: "Specificity of the N1 and N2 sialidase subtypes from human-influenza A virus for naturally occurring and synthetic gangliosides." Glycobiology. 8. 527-532 (1998)

[Publications] Kaneda,K: "Infectivity and arthritis-induction of Borrelia japonica on SCID mice and immune competent mice: possible role of galactosylceramide binding activity on initiation of infection" Microbiol.Immunol.42(3). 171-175 (1998)

[Publications] Kamitakahara,H.: "Lysoganglioside/poly-L-glutamic acid conjugate as picomolar inhibitor of influenza hemagglutinin" Angew.Chem,Int.Ed.Engl.110(11). 1524-1528 (1998)

[Publications] Ryan-Poirier,K.,: "Changes in H3 influenza A virus receptor specificity during replication in humans." Virus Res.56. 169-176 (1998)

[Publications] Miyamoto,D.,: "Thuaplicin-copper chelates inhibit replication of human influenza viruses" Antiviral Res.39. 89-100 (1998)

[Publications] Hosaka,Y.: "Binding of influenza and paramyxoviruses to group B Streptococcus with the terminal sialyl-galactose linkage. ,169-174(1998)." J.Electron Microscopy. 47(2). 169-174 (1998)

[Publications] Ikeda,K.: "Chemoenzymaticsynthesis of an N-acetylneuraminic acid analogue having a carbamoylmethylgroup at C-4 as an inhibitor of sialidase from influenza virus.312,183-189(1998)." Carbohydrate Res.312. 183-189 (1998)

[Publications] Tsuchida,A.: "Simple synthesis of sialyllactose-carrying polystylene and its binding with influenza virus." Glycoconjugate J.No.11(in press). (1999)

[Publications] Shikata,K.: "L-selectin and its ligands mediate the infiltration of mononuclear cells into kidney interstitium after ureteral obstruction." Am.J.Pathol.(in press). (1999)

[Publications] 鈴木康夫: "インフルエンザウイルスレセプター破壊酵素、ノイラミニダーゼ(NA)のウイルス出芽における役割" 日本臨床、特集:インフルエンザウイルス感染の分子病理学. 特集号. 162-167 (1997)

[Publications] 鈴木康夫: "インフルエンザウイルスの宿主域とレセプター特異性" 日本臨床、特集:インフルエンザウイルス感染の分子病理学. 特集号. 142-149 (1997)

[Publications] 鈴木康夫: "インフルエンザウイルスの感染と糖鎖" バイオインダストリー. 55(4). 37-38 (1997)

[Publications] 鈴木康夫: "セレクチンのリガンド" 炎症と免疫. 5(5). 494-503 (1997)

[Publications] 鈴木康夫: "Ligands for Selectins" 動脈硬化. 25(3). 105-112 (1997)

[Publications] 鈴木康夫: "インフルエンザウイルスの宿主域変異の分子機構" ファルマシア. 34(6). 678-683 (1998)

[Publications] 鈴木康夫: "インフルエンザウイルスと糖鎖認識" 蛋白質核酸酵素、特集「糖鎖生物学」. 43(12). 1112-1118 (1998)

[Publications] 鈴木康夫(共著): "感染症実験講座" 丸善, 367 (1998)

鈴木康夫静岡県立大学, 薬学部, 教授 (00046278)