Structures and Receptor Binding of Hemagglutinins from Human-Infecting H7N9 Influenza Viruses

Structures and Receptor Binding of Hemagglutinins from Human-Infecting H7N9 Influenza Viruses
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DOI:
10.1126/science.1242917
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发表时间:
2013-10-11
期刊:
影响因子:
56.9
通讯作者:
Gao, George F.
Gao, George F.
中科院分区:
综合性期刊1区
文献类型:
--
作者:
Shi, Yi;Zhang, Wei;Gao, George F.

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最近在中国发现了一种禽源性人感染流感(H7N9)病毒。我们已经评估了两种人H7N9分离株A/Shanghai/1/2013(SH-H7N9)(含有禽类特征残基Gln(226))和A/Anhui/1/2013(AH-H7N9)(含有禽类特征残基Leu(226))的病毒血凝素(HA)受体结合特性。我们发现SH-H7N9 HA优先结合禽类受体类似物,而AH-H7N9 HA结合禽类和人受体类似物。此外,发现AH-H7N9突变体HA(Leu(226)-> Gln)表现出双重受体结合特性,表明其他氨基酸取代有助于受体结合开关。SH-H7N9 HA、AH-H7N9 HA及其突变体与禽类或人受体类似物复合的结构显示AH-H7N9如何结合人受体,同时仍保留禽类受体结合特性。
An avian-origin human-infecting influenza (H7N9) virus was recently identified in China. We have evaluated the viral hemagglutinin (HA) receptor-binding properties of two human H7N9 isolates, A/Shanghai/1/2013 (SH-H7N9) (containing the avian-signature residue Gln(226)) and A/Anhui/1/2013 (AH-H7N9) (containing the mammalian-signature residue Leu(226)). We found that SH-H7N9 HA preferentially binds the avian receptor analog, whereas AH-H7N9 HA binds both avian and human receptor analogs. Furthermore, an AH-H7N9 mutant HA (Leu(226) -> Gln) was found to exhibit dual receptor-binding property, indicating that other amino acid substitutions contribute to the receptor-binding switch. The structures of SH-H7N9 HA, AH-H7N9 HA, and its mutant in complex with either avian or human receptor analogs show how AH-H7N9 can bind human receptors while still retaining the avian receptor-binding property.