Consequences of in vitro host shift for St. Louis encephalitis virus

Consequences of in vitro host shift for St. Louis encephalitis virus
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DOI:
10.1099/vir.0.063545-0
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发表时间:
2014-06-01
影响因子:
3.8
通讯作者:
Kramer, Laura D.
Kramer, Laura D.
中科院分区:
医学3区
文献类型:
--
作者:
Ciota, Alexander T.;Payne, Anne F.;Kramer, Laura D.

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了解RNA病毒的宿主范围转移和扩展的可能性对于预测这些病原体的进化和流行病学路径至关重要:由于节肢动物传播的病毒(虫媒病毒)在其扩增周期中经历频繁的溢出,并且本质上是通才,它们可能在一系列宿主环境中经历相对较高的成功频率。尽管如此,对于虫媒病毒来说,宿主扩展的潜力、适应新环境的遗传相关性以及这种适应在原本有能力的宿主中的成本仍然没有得到充分的表征。在这里提出的研究中,我们利用圣路易斯脑炎病毒(SLEV;黄病毒科,黄病毒属)的实验进化,在体外的安德氏皮肤enteror蜱细胞系中模拟适应一种新的无脊椎动物宿主。我们的研究结果表明,在不同的谱系中,交替宿主的适应水平和成本是高度可变的,但蜱虫细胞的适应性显著提高是可以实现的,只需对共识基因序列进行适度的改变。此外,尽管多样性的积累有时可以缓冲SLEV群体内的表型成本,但随着蜱虫细胞传代,在脊椎动物细胞培养中感染和传播能力受损的变异比例增加。这些变异子集的分离和特征表明NS3基因是SLEV的重要宿主范围决定因素。
Understanding the potential for host range shifts and expansions of RNA viruses is critical to predicting the evolutionary and epidemiological paths of these pathogens: As arthropod-borne viruses (arboviruses) experience frequent spillover from their amplification cycles and are generalists by nature, they are likely to experience a relatively high frequency of success in a range of host environments. Despite this, the potential for host expansion, the genetic correlates of adaptation to novel environments and the costs of such adaptations in originally competent hosts are still not characterized fully for arboviruses. In the studies presented here, we utilized experimental evolution of St. Louis encephalitis virus (SLEV; family Flaviviridae, genus Flavivirus) in vitro in the Dermacentor andersoni line of tick cells to model adaptation to a novel invertebrate host. Our results demonstrated that levels of adaptation and costs in alternate hosts are highly variable among lineages, but also that significant fitness increases in tick cells are achievable with only modest change in consensus genetic sequence. In addition, although accumulation of diversity may at times buffer against phenotypic costs within the SLEV swarm, an increased proportion of variants with an impaired capacity to infect and spread on vertebrate cell culture accumulated with tick cell passage. Isolation and characterization of a subset of these variants implicates the NS3 gene as an important host range determinant for SLEV.