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首页> 外文期刊>Proceedings of the National Academy of Sciences of the United States of America >Bottleneck-mediated quasispecies restriction during spread of an RNA virus from inoculation site to brain
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Bottleneck-mediated quasispecies restriction during spread of an RNA virus from inoculation site to brain

机译：RNA病毒从接种部位向大脑传播过程中瓶颈介导的准种限制

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摘要

The amplification of RNA viruses such as poliovirus is associated with high error rates, and the resulting diversity likely facilitates viral survival within an infected host. However, within individual tissues of infected hosts, there may be barriers to viral spread that limit genome sampling. We tested whether poliovirus population diversity was maintained during viral spread to the brain of poliovirus receptor-expressing mice. Each of four restriction enzyme site-tagged viruses was shown to be able to replicate in the mouse brain. However, when infection was initiated by i.m., i.v., or i.p. routes, only a subset of the members of the injected pool was detectable in the brain. This jackpot effect was the result of a bottleneck in viral transit from the inoculation site to the brain. The bottleneck was difficult to overcome, requiring a 10(7) increase in viral inoculum to allow representation of all or most members of the infecting pool. Therefore, the bottleneck is not likely to be a physical barrier but an antiviral state induced by a founder virus. We suggest that the innate immune response can limit viral pathogenicity by limiting the number and therefore the diversity of viruses during spread to vulnerable tissues.
机译：RNA病毒（如脊髓灰质炎病毒）的扩增与较高的错误率相关，并且所产生的多样性可能有助于感染宿主内的病毒存活。但是，在受感染宿主的单个组织内，可能存在病毒传播的障碍，从而限制了基因组采样。我们测试了在脊髓灰质炎病毒受体表达小鼠的脑部病毒传播过程中是否保持了脊髓灰质炎病毒种群多样性。四种限制性酶位点标记的病毒中的每一种都能够在小鼠大脑中复制。但是，当感染是由i.m.，i.v。或i.p.发起时。路线中，大脑中仅可检测到注入池成员的一个子集。这种累积奖金效应是病毒从接种部位向大脑转移的瓶颈所致。瓶颈很难克服，需要病毒接种量增加10（7），才能代表感染池的所有或大多数成员。因此，瓶颈不太可能是物理障碍，而是由Founder病毒诱导的抗病毒状态。我们建议先天的免疫反应可以通过限制病毒传播到易感染组织的数量，从而限制病毒的致病性。

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