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首页> 外文期刊>Journal of Clinical Microbiology >Enhanced Expression of an α2,6-Linked Sialic Acid on MDCK Cells Improves Isolation of Human Influenza Viruses and Evaluation of Their Sensitivity to a Neuraminidase Inhibitor
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Enhanced Expression of an α2,6-Linked Sialic Acid on MDCK Cells Improves Isolation of Human Influenza Viruses and Evaluation of Their Sensitivity to a Neuraminidase Inhibitor

机译：MDCK细胞上α2，6-连接的唾液酸的增强表达改善了人类流感病毒的分离和对神经氨酸酶抑制剂的敏感性评估

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The extensive use of neuraminidase (NA) inhibitors to treat influenza virus infections mandates close monitoring for resistant variants. Cultured cells do not provide a reliable means of evaluating the susceptibility of human influenza virus isolates to NA inhibitors. That is, the growth of such viruses in cell lines (e.g., Madin-Darby canine kidney [MDCK] cells) is not inhibited by these drugs, even though their sialidase activity is drug-sensitive. Matrosovich et al. (J. Virol. >77:8418-8425, 2003) showed that an MDCK cell line overexpressing the human β-galactoside α2,6-sialyltransferase I (ST6Gal I) gene has the potential to assess the sensitivity of human influenza virus isolates to NA inhibitors, based on studies with a limited number of viruses. Here, we asked whether clinical isolates of influenza virus are universally sensitive to an NA inhibitor (oseltamivir) in an MDCK cell line expressing the ST6Gal I gene. The sensitivity of viruses to oseltamivir correlated with the sensitivity of viral sialidase to the compound, demonstrating the potential utility of this modified cell line for detecting NA inhibitor-resistant viruses. Moreover, in ST6Gal I-overexpressing cells, the growth of human influenza viruses was up to 2 logs higher than in MDCK cells. We conclude that the human ST6Gal I-expressing MDCK cell line is useful not only for evaluating their sensitivity to NA inhibitors, but also for isolation of influenza viruses from clinical samples.
机译：神经氨酸酶（NA）抑制剂广泛用于治疗流感病毒感染，要求对耐药性变体进行密切监测。培养的细胞不提供评估人流感病毒分离株对NA抑制剂敏感性的可靠方法。即，即使这些病毒的唾液酸酶活性是药物敏感性的，这些病毒在细胞系（例如，Madin-Darby犬肾[MDCK]细胞）中的生长也不受其抑制。 Matrosovich等。 （J. Virol。> 77： 8418-8425，2003）表明，过表达人β-半乳糖苷α2,6-唾液酸转移酶I（ST6Gal I）基因的MDCK细胞系有可能评估敏感性根据对有限数量的病毒的研究，将人类流感病毒分离株分离为NA抑制剂。在这里，我们询问流感病毒的临床分离株是否对表达ST6Gal I基因的MDCK细胞系中的NA抑制剂（oseltamivir）普遍敏感。病毒对奥司他韦的敏感性与病毒唾液酸酶对该化合物的敏感性相关，证明了这种修饰的细胞系在检测抗NA抑制剂的病毒中的潜在用途。此外，在过表达ST6Gal I的细胞中，人流感病毒的生长比MDCK细胞中的生长高2个对数。我们得出的结论是，表达人ST6Gal I的MDCK细胞系不仅可用于评估其对NA抑制剂的敏感性，还可用于从临床样品中分离流感病毒。

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