Bottleneck-mediated quasispecies restriction during spread of an RNA virus from inoculation site to brain
Bottleneck-mediated quasispecies restriction during spread of an RNA virus from inoculation site to brain
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DOI：
10.1073/pnas.0600834103
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发表时间：
2006-04-04
影响因子：
11.1
通讯作者：
Kirkegaard, K
中科院分区：
文献类型：
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作者：
Pfeiffer, JK;Kirkegaard, K
RNA病毒（如脊髓灰质炎病毒）的扩增与高错误率相关，由此产生的多样性可能有助于病毒在受感染宿主内的存活。然而，在受感染宿主的个体组织内，可能存在限制基因组采样的病毒传播障碍。我们测试了脊髓灰质炎病毒种群多样性是否在病毒传播到脊髓灰质炎病毒受体表达小鼠的大脑期间得以维持。四种限制性内切酶位点标记的病毒中的每一种都被证明能够在小鼠大脑中复制。然而，当感染是通过肌内注射开始时，静脉注射，或腹膜内途径，在脑中仅可检测到注射池成员的子集。这种头奖效应是病毒从接种部位到大脑的运输瓶颈的结果。瓶颈难以克服，需要病毒接种物增加10（7），以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屏障，而是创始者病毒诱导的抗病毒状态。我们认为，先天免疫反应可以限制病毒的致病性，通过限制数量，因此在传播到脆弱组织的病毒的多样性。
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.