Role of the mutant spectrum in adaptation and replication of West Nile virus

Role of the mutant spectrum in adaptation and replication of West Nile virus
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DOI:
10.1099/vir.0.82606-0
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发表时间:
2007-03-01
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.;Ngo, Kiet A.;Kramer, Laura D.

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自1999年引入北美以来,西尼罗河病毒(WNV)已成功传播到美国,加拿大,墨西哥,加勒比海地区以及中美洲和南美洲的部分地区。尽管感染了广泛的蚊子和鸟类,但该病毒在遗传上仍然高度保守。这种在空间和时间上缺乏进化变化的现象在许多虫媒病毒中很常见,通常归因于脊椎动物宿主和无脊椎动物载体之间病毒循环产生的适应性约束。像迄今为止研究的大多数RNA病毒一样,WNV在自然界中已被证明是一种高度遗传多样性的基因型群体。很少有研究直接评估这些突变谱在病毒适应性和适应性中的作用。利用克隆分析和反向遗传学实验,本研究评估了基因型多样性和共识变化的重要性,在产生适应性表型的西尼罗河病毒后,连续蚊子细胞传代。结果表明,蚊子细胞中WNV复制能力的增加与突变谱大小的增加相关,并且一致性变化不仅仅是WNV病毒适应性和适应性改变的原因。这些数据提供了证据的重要性,准种动态的黄病毒适应新的和不断变化的环境和主机,几乎没有证据表明显着的遗传变化。
West Nile virus (WNV) has successfully spread throughout the USA, Canada, Mexico, the Caribbean and parts of Central and South America since its 1999 introduction into North America. Despite infecting a broad range of both mosquito and avian species, the virus remains highly genetically conserved. This lack of evolutionary change over space and time is common with many arboviruses and is frequently attributed to the adaptive constraints resulting from the virus cycling between vertebrate hosts and invertebrate vectors. WNV, like most RNA viruses studied thus far, has been shown in nature to exist as a highly genetically diverse population of genotypes. Few studies have directly evaluated the role of these mutant spectra in viral fitness and adaptation. Using clonal analysis and reverse genetics experiments, this study evaluated genotype diversity and the importance of consensus change in producing the adaptive phenotype of WNV following sequential mosquito cell passage. The results indicated that increases in the replicative ability of WNV in mosquito cells correlate with increases in the size of the mutant spectrum, and that consensus change is not solely responsible for alterations in viral fitness and adaptation of WNV. These data provide evidence of the importance of quasispecies dynamics in the adaptation of a flavivirus to new and changing environments and hosts, with little evidence of significant genetic change.