Cooperation between distinct viral variants promotes growth of H3N2 influenza in cell culture.
Cooperation between distinct viral variants promotes growth of H3N2 influenza in cell culture.
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DOI：
10.7554/elife.13974
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发表时间：
2016-03-15
期刊：
影响因子：
7.7
通讯作者：
Bloom JD
中科院分区：
文献类型：
--
作者：
Xue KS;Hooper KA;Ollodart AR;Dingens AS;Bloom JD
RNA病毒迅速分化成相关基因型的准种。这种遗传多样性长期以来一直被认为有助于适应，但最近的研究表明，变异之间的合作也可能增加种群适应性。在这里，我们证明了两种H3 N2流感病毒变体之间的强有力的合作，这两种变体的不同之处在于神经氨酸酶残基151处的单一突变，神经氨酸酶通常介导病毒从宿主细胞中退出。残基151在测序的分离株中通常被注释为模糊的氨基酸，表明混合的病毒群体。我们表明，混合种群生长优于任何一个变种单独在细胞培养。任何一种变异的纯群体通过突变产生另一种变异，然后稳定地保持两种基因型的混合。我们认为，合作的出现，因为混合人口结合联合收割机一个变异的熟练程度在细胞入口与其他的熟练程度在细胞出口。我们的工作证明了病毒准种中定义的变体之间存在特定的合作相互作用。http://dx.doi.org/10.7554/eLife.13974.001像流感这样的病毒变异很快。当你患上流感时，病毒会劫持你的细胞，你的身体成为数百万病毒的家园，其中许多病毒在基因上彼此不同。以前的研究表明，快速进化的病毒变体有时会相互合作以生存，但很少有研究指出特定的合作相互作用。在过去的十年中，流感监测小组注意到，当流感病毒在实验室中生长时，一种特定的突变病毒反复出现。Xue等人认为，这种突变病毒不应该能够自行生长，因为突变破坏了流感病毒用于从宿主细胞分离的蛋白质。于是，他们询问变异体是否与未变异的病毒合作生存。Xue等人揭示，这两种流感病毒只有一个突变不同，当在实验室的细胞中生长时，它们会相互合作。突变病毒通常在非突变病毒群体中随机突变后出现，反之亦然。这两种病毒并没有相互竞争，直到一种病毒灭绝，相反，这两种病毒实际上在一起比分开时生长得更好。Xue等人认为，这是因为其中一种病毒擅长进入新细胞，而另一种病毒更擅长离开细胞传播感染。混合种群结合了这两种优势。在这项工作之后，仍然不清楚流感病毒是否在其他环境中合作-例如，在人类感染期间。还需要进一步的研究来确定这两种病毒在分子水平上如何相互帮助。DOI：http://dx.doi.org/10.7554/eLife.13974.002网站
RNA viruses rapidly diversify into quasispecies of related genotypes. This genetic diversity has long been known to facilitate adaptation, but recent studies have suggested that cooperation between variants might also increase population fitness. Here, we demonstrate strong cooperation between two H3N2 influenza variants that differ by a single mutation at residue 151 in neuraminidase, which normally mediates viral exit from host cells. Residue 151 is often annotated as an ambiguous amino acid in sequenced isolates, indicating mixed viral populations. We show that mixed populations grow better than either variant alone in cell culture. Pure populations of either variant generate the other through mutation and then stably maintain a mix of the two genotypes. We suggest that cooperation arises because mixed populations combine one variant’s proficiency at cell entry with the other’s proficiency at cell exit. Our work demonstrates a specific cooperative interaction between defined variants in a viral quasispecies. DOI: http://dx.doi.org/10.7554/eLife.13974.001 Viruses like influenza mutate fast. When you get the flu, the virus hijacks your cells, and your body becomes home to millions of viruses, many of which are genetically different from each other. Previous research had suggested that variants of rapidly evolving viruses sometimes cooperate with one another to survive, but few studies have pinpointed specific cooperative interactions. In the past decade, influenza surveillance groups noticed that one particular mutant virus appears again and again when influenza viruses are grown in the laboratory. Xue et al. thought that this mutant virus shouldn’t be able to grow on its own because the mutation disrupted the protein that influenza viruses use to detach from host cells. So, they asked if the mutant was cooperating with the non-mutated virus to survive. Xue et al. revealed that the two influenza viruses, which differ by just one mutation, cooperate with each other when grown in cells in the laboratory. The mutant virus often appeared following a random mutation in a population of non-mutated virus, and vice versa. Instead of competing with each other until one virus went extinct, the two viruses actually grew better together than they did apart. Xue et al. suggest that this is because one of the viruses is good at entering new cells, while the other is better at exiting cells to spread the infection. A mixed population combines these two strengths. Following on from this work, it remains unclear whether influenza viruses cooperate in other settings – for example, during infections in people. Further studies are also needed to determine exactly how the two viruses help each other at the molecular level. DOI: http://dx.doi.org/10.7554/eLife.13974.002