表型混合和隐藏可能有助于病毒准种的记忆
Phenotypic mixing and hiding may contribute to memory in viral quasispecies
摘要：
背景在最近对口蹄疫病毒进行的一些实验中，发现一种有害的突变体可以避免灭绝，并在种群中长期存在。这种观察被称为准种记忆。准种记忆的起源还没有完全弄清楚。结果我们提出并分析了一个简单的野生型病毒和突变体之间的互补模型，该突变体具有受损的细胞进入能力。除非通过突变从野生型中重新产生突变体，否则突变体将灭绝。然而，在表型混合和隐藏作为一种互补机制，在没有突变的情况下，灭绝的时间随着感染复数（m.o.i.）增加而增加。在选择-突变平衡下，突变体的平衡频率也随着m.o.i.的增加而增加。在高犯罪率下，大部分突变体基因组被野生型蛋白质包被，这使得它们能够像野生型病毒体一样有效地感染细胞，从而增加它们对野生型水平的适应性。此外，即使在低m.o.i.突变体的平衡频率高于标准准种模型所预测的，因为从野生型亲本产生的一部分突变体病毒体也将被野生型蛋白质所取代。结论.我们的模型预测，表型隐藏将强烈影响病毒的种群动态，特别是在高m.o.i.，并且在低m.o.i.下也将对突变-选择平衡具有重要影响。突变灭绝的延迟和突变频率的增加，在平衡可能，至少部分地解释准种种群的记忆。
英文摘要：
Background. In a number of recent experiments with food-and-mouth disease virus, a deleterious mutant, was found to avoid extinction and remain in the population for long periods of time. This observation was called quasispecies memory. The origin of quasispecies memory is not fully understood. Results. We propose and analyze a simple model of complementation between the wild type virus and a mutant that has an impaired ability of cell entry. The mutant will go extinct unless it is recreated from the wild type through mutations. However, under phenotypic mixing-and-hiding as a mechanism of complementation, the time to extinction in the absence of mutations increases with increasing multiplicity of infection (m.o.i.). The mutant's frequency at equilibrium under selection-mutation balance also increases with increasing m.o.i. At high m.o.i., a large fraction of mutant genomes are encapsidated with wild-type protein, which enables them to infect cells as efficiently as the wild type virions, and thus increases their fitness to the wild-type level. Moreover, even at low m.o.i. the equilibrium frequency of the mutant is higher than predicted by the standard quasispecies model, because a fraction of mutant virions generated from wild-type parents will also be encapsidated by wild-type protein. Conclusions. Our model predicts that phenotypic hiding will strongly influence the population dynamics of viruses, particularly at high m.o.i., and will also have important effects on the mutation--selection balance at low m.o.i. The delay in mutant extinction and increase in mutant frequencies at equilibrium may, at least in part, explain memory in quasispecies populations.
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