ヒトに感染するH7N9型インフルエンザウイルスのヘマグルチニンの構造と受容体結合
1Research Network of Immunity and Health, Beijing Institutes of Life Science, Chinese Academy of Sciences, Beijing, China.
Science (New York, N.Y.)
|September 7, 2013
まとめ
鳥類起源のH7N9インフルエンザウイルスは,様々な受容体結合を示す. ある分離体が鳥類受容体を好む一方で,別の分離体は鳥類受容体とヒト受容体の両方に結合し,ヒトへの感染への適応性を示しています.
科学分野:
- ウイルス学 ウイルス学 ウイルス学
- 分子生物学は分子生物学である.
- 構造生物学 構造生物学とは
背景:
- 中国では,ヒトに感染できる新型鳥類インフルエンザA (H7N9) ウイルスが出現した.
- ウイルスのヘマグルチニン (HA) 受容体結合特性を理解することは,パンデミックの可能性を評価するために重要である.
研究 の 目的:
- 2つのヒトH7N9インフルエンザウイルス単離体の受容体結合特性を調査する.
- H7N9ウイルスの異なる受容体結合の構造的基礎を解明する.
主な方法:
- ヘマグルチニン (HA) 受容体結合特性の比較分析. H7N9 ウイルスの単離体.
- 鳥類およびヒトの受容体類似体との複合体におけるHAの構造的研究.
- サイト指向型ミュータゲネシスで,受容体結合に対するアミノ酸の貢献度を評価する.
主要な成果:
- A/Shanghai/1/2013 (SH-H7N9) HA with Gln(226) は,鳥類の受容体に優位に結合しています.
- A/Anhui/1/2013 (AH-H7N9) HA with Leu(226) は,鳥類とヒトの受容体への二重結合を示しています.
- 構造分析により,AH-H7N9 HAがヒトの受容体 afinity を獲得しながら,鳥類の受容体結合を維持する方法が明らかになりました.
結論:
- AH-H7N9 HAに含まれるレウ226の残留は,鳥類の受容体と並行して,ヒトの受容体への結合を促進する.
- 位置226を超えるアミノ酸の置換は,H7N9ウイルスの受容体結合スイッチに寄与する.
- H7N9ウイルスは,ヒトの呼吸道受容体に適応する能力を持っています.
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