Presence of Oseltamivir-Resistant Pandemic A/H1N1 Minor Variants Before Drug Therapy With Subsequent Selection and Transmission
Presence of Oseltamivir-Resistant Pandemic A/H1N1 Minor Variants Before Drug Therapy With Subsequent Selection and Transmission
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DOI：
10.1093/infdis/jis571
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发表时间：
2012-11-15
影响因子：
6.4
通讯作者：
Boivin, Guy
中科院分区：
文献类型：
--
作者：
Ghedin, Elodie;Holmes, Edward C.;Boivin, Guy
一小部分（1%-1.5%）2009年大流行性流感A/H1N1病毒株（A[H1N1] pdm 09）对奥司他韦耐药，几乎完全是因为神经氨酸酶蛋白中的H275 Y突变。然而，许多感染耐药菌株的人没有接受抗病毒药物治疗。抗药性病毒是否在未治疗的个体中最初作为微小变异体存在，然后才成为病毒群体中的优势菌株，对于预测抗药性产生的速度非常重要。为了解决这个问题，我们对来自免疫功能低下儿童和家庭爆发中的2名个体的系列鼻咽标本的病毒群进行了超深度测序。我们观察到Y275突变在治疗开始前在感染宿主中作为微小变异存在。我们还发现了这种耐药变异与药物敏感病毒传播的证据。这些观察结果提供了关于在没有奥司他韦治疗的情况下Y275突变的相对适合性的重要信息。
A small proportion (1%-1.5%) of 2009 pandemic influenza A/H1N1 virus strains (A[H1N1]pdm09) are oseltamivir resistant, almost exclusively because of a H275Y mutation in the neuraminidase protein. However, many individuals infected with resistant strains had not received antivirals. Whether drug-resistant viruses are initially present as minor variants in untreated individuals before they emerge as the dominant strain in a virus population is of great importance for predicting the speed at which resistance will arise. To address this issue, we used ultra-deep sequencing of viral populations from serial nasopharyngeal specimens from an immunocompromised child and from 2 individuals in a household outbreak. We observed that the Y275 mutation was present as a minor variant in infected hosts before the onset of therapy. We also found evidence for the transmission of this drug-resistant variant with drug-susceptible viruses. These observations provide important information on the relative fitness of the Y275 mutation in the absence of oseltamivir treatment.