Cooperating H3N2 Influenza Virus Variants Are Not Detectable in Primary Clinical Samples.
Cooperating H3N2 Influenza Virus Variants Are Not Detectable in Primary Clinical Samples.
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在主要临床样本中无法检测到 H3N2 流感病毒协同变异体。
DOI：
10.1128/mspheredirect.00552-17
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发表时间：
2018
期刊：
影响因子：
4.8
通讯作者：
Bloom,JesseD
中科院分区：
文献类型：
--
作者：
Xue,KatherineS;Greninger,AlexanderL;Pérez-Osorio,Ailyn;Bloom,JesseD
RNA病毒的高突变率导致快速的遗传多样化，这可以使病毒群体中的变体之间的合作相互作用成为可能。我们先前描述了两种不同的H3N2流感病毒变异体，它们在细胞培养中协同作用。这些变体的区别在于神经氨酸酶蛋白中的单一突变D151G。当病毒在细胞培养物中传代时，D151G突变达到约50%的稳定频率。然而，目前尚不清楚D151G的协同效益的选择是否是一种细胞培养现象，或者这种突变是否有时也以可观的频率存在于直接从受感染的人中取样的病毒群体中。先前的工作尚未在未传代的临床样本中检测到D151 G，但这些研究使用了桑格测序和焦磷酸测序等方法，这些方法对低频变异相对不敏感。我们鉴定了2013年至2015年期间收集的9份人H3N2流感病毒样本，其中桑格测序在细胞培养物中传代1至3次后检测到高频率的D151 G突变。我们对未传代的临床样本进行深度测序，以识别低频病毒变体。D151G的频率不超过任何测序样品中文库制备和测序错误的频率。我们的结论是，在细胞培养中的通道是主要负责的D151G在最近的H3N2流感病毒strains.IMPORTANCEViruses频繁观察突变迅速，最近的研究表明，RNA病毒相关的病毒变种有时可以合作，以提高彼此的增长。我们先前描述了H3N2流感病毒的两种变体，它们在细胞培养中协同作用。当流感病毒的人类样本在测序之前在实验室中生长时，经常观察到负责合作的突变，但目前尚不清楚这种突变是否也存在于人类感染中，或者仅仅是实验室传代的结果。我们鉴定了9株人类流感病毒分离株，它们在实验室中生长后发生了协同突变，并对未传代的临床样本进行了高度敏感的深度测序，以确定突变是否存在于原始的人类感染中。我们在未传代的样品中没有发现合作突变的证据，这表明合作主要是在实验室条件下产生的。
The high mutation rates of RNA viruses lead to rapid genetic diversification, which can enable cooperative interactions between variants in a viral population. We previously described two distinct variants of H3N2 influenza virus that cooperate in cell culture. These variants differ by a single mutation, D151G, in the neuraminidase protein. The D151G mutation reaches a stable frequency of about 50% when virus is passaged in cell culture. However, it is unclear whether selection for the cooperative benefits of D151G is a cell culture phenomenon or whether the mutation is also sometimes present at appreciable frequency in virus populations sampled directly from infected humans. Prior work has not detected D151G in unpassaged clinical samples, but those studies have used methods like Sanger sequencing and pyrosequencing, which are relatively insensitive to low-frequency variation. We identified nine samples of human H3N2 influenza virus collected between 2013 and 2015 in which Sanger sequencing had detected a high frequency of the D151G mutation following one to three passages in cell culture. We deep sequenced the unpassaged clinical samples to identify low-frequency viral variants. The frequency of D151G did not exceed the frequency of library preparation and sequencing errors in any of the sequenced samples. We conclude that passage in cell culture is primarily responsible for the frequent observations of D151G in recent H3N2 influenza virus strains.IMPORTANCEViruses mutate rapidly, and recent studies of RNA viruses have shown that related viral variants can sometimes cooperate to improve each other’s growth. We previously described two variants of H3N2 influenza virus that cooperate in cell culture. The mutation responsible for cooperation is often observed when human samples of influenza virus are grown in the lab before sequencing, but it is unclear whether the mutation also exists in human infections or is exclusively the result of lab passage. We identified nine human isolates of influenza virus that had developed the cooperating mutation after being grown in the lab and performed highly sensitive deep sequencing of the unpassaged clinical samples to determine whether the mutation existed in the original human infections. We found no evidence of the cooperating mutation in the unpassaged samples, suggesting that the cooperation arises primarily under laboratory conditions.
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DOI：
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发表时间：
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期刊：
The Yale Journal of Biology and Medicine
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期刊：
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