Characterization of 2 influenza A(H3N2) clinical isolates with reduced susceptibility to neuraminidase inhibitors due to mutations in the hemagglutinin gene
Characterization of 2 influenza A(H3N2) clinical isolates with reduced susceptibility to neuraminidase inhibitors due to mutations in the hemagglutinin gene
复制标题
DOI：
10.1086/344237
复制
发表时间：
2002-10-15
影响因子：
6.4
通讯作者：
Boivin, G
中科院分区：
文献类型：
--
作者：
Abed, Y;Bourgault, AM;Boivin, G
以往的研究表明，流感病毒血凝素（HA）基因的氨基酸变化可能会导致体外神经氨酸酶抑制剂（NAIs）的敏感性降低。然而，这种HA变体在临床环境中的出现和特征仍然缺乏研究。在此，我们报告了2株来自未经治疗的患者的甲型流感（H3 N2）分离株，其HA 1基因中存在Arg 229-->Ile取代。在神经氨酸酶抑制试验中，Ile 229变异体对扎那米韦和奥司他韦的敏感性与Arg 229病毒相同，但在基于细胞的试验中敏感性显著降低（60-140倍）。虽然Ile 229变体在动态结合试验中对Madin-Darby犬肾（MDCK）细胞的吸附效率较低，但它们在雪貂中对扎那米韦仍然非常敏感。我们的研究显示了HA 1 229残基在病毒与MDCK细胞结合中的重要性，并证实了基于细胞的测定在预测HA变体对NAI的体内易感性方面的不可靠性。
Previous studies have shown that amino acid changes in the hemagglutinin (HA) gene of influenza viruses may result in decreased susceptibility to neuraminidase inhibitors (NAIs) in vitro. However, the emergence and characteristics of such HA variants in the clinical setting remain poorly studied. Herein, we report 2 influenza A(H3N2) isolates, from untreated patients, harboring an Arg229-->Ile substitution in the HA1 gene. The Ile229 variants were as sensitive as the Arg229 viruses to zanamivir and oseltamivir in neuroaminidase inhibition assays but were significantly less susceptible (by 60-140-fold) in cell-based assays. Although the Ile229 variants adsorbed less efficiently to Madin-Darby canine kidney (MDCK) cells in kinetic binding assays, they remained very sensitive to zanamivir in ferrets. Our study shows the importance of the HA1 229 residue in virus binding to MDCK cells and confirms the unreliability of cell-based assays in predicting the in vivo susceptibility of HA variants to NAIs.