Altered Receptor Specificity and Cell Tropism of D222G Hemagglutinin Mutants Isolated from Fatal Cases of Pandemic A(H1N1) 2009 Influenza Virus
Altered Receptor Specificity and Cell Tropism of D222G Hemagglutinin Mutants Isolated from Fatal Cases of Pandemic A(H1N1) 2009 Influenza Virus
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DOI：
10.1128/jvi.01639-10
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发表时间：
2010-11-01
影响因子：
5.4
通讯作者：
Matrosovich, Mikhail
中科院分区：
文献类型：
--
作者：
Liu, Yan;Childs, Robert A.;Matrosovich, Mikhail
偶尔检测到2009年甲型H1N1流感病毒血凝素受体结合位点的突变。Asp 222 Gly（D222 G）取代与重度或致死性疾病相关。在这里，我们表明，222 G变异感染的比例较高的纤毛细胞在培养的人气道上皮细胞比病毒与222 D或222 E，主要针对无纤毛细胞。碳水化合物微阵列分析表明，222 G变体结合更广泛的α 2-3-连接的唾液酸受体序列的类型上表达的纤毛支气管上皮细胞和肺内的上皮细胞。222 G突变体的这些特征可能有助于疾病的恶化。
Mutations in the receptor-binding site of the hemagglutinin of pandemic influenza A(H1N1) 2009 viruses have been detected sporadically. An Asp222Gly (D222G) substitution has been associated with severe or fatal disease. Here we show that 222G variants infected a higher proportion of ciliated cells in cultures of human airway epithelium than did viruses with 222D or 222E, which targeted mainly nonciliated cells. Carbohydrate microarray analyses showed that 222G variants bind a broader range of alpha 2-3-linked sialyl receptor sequences of a type expressed on ciliated bronchial epithelial cells and on epithelia within the lung. These features of 222G mutants may contribute to exacerbation of disease.