West Nile Virus Temperature Sensitivity and Avian Virulence Are Modulated by NS1-2B Polymorphisms.
West Nile Virus Temperature Sensitivity and Avian Virulence Are Modulated by NS1-2B Polymorphisms.
复制标题
西尼罗河病毒温度敏感性和禽类毒力受到NS1-2B多态性的调节。
DOI：
10.1371/journal.pntd.0004938
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发表时间：
2016-08
影响因子：
3.8
通讯作者：
Brault AC
中科院分区：
文献类型：
--
作者：
Dietrich EA;Langevin SA;Huang CY;Maharaj PD;Delorey MJ;Bowen RA;Kinney RM;Brault AC
西尼罗河病毒（WNV）在多种鸟类中复制，这些鸟类是储存和扩增宿主。在北美分离的WNV菌株，如原型菌株NY 99，在某些鸟类物种中引起高致病性应答，特别是美洲乌鸦（AMCR;短喙乌鸦）。相比之下，在肯尼亚分离的密切相关的菌株KN 3829在AMR中表现出低病毒血症应答和有限的死亡率。先前的工作已经将致病性的差异主要与NS 3蛋白的解旋酶结构域中的位置249处的单个氨基酸突变相关联。NY 99菌株在该位置编码脯氨酸残基，而KN 3829编码苏氨酸。在KN 3829遗传背景中引入NS 3-T249 P突变显著增加了毒力和死亡率;然而，峰值病毒血症和死亡率低于NY 99。为了阐明不包括NS 3 -249多态性的表型变异的病毒遗传基础，创建了嵌合NY 99/KN 3829病毒。我们在此表明，在NS 1 -2B区域的差异有助于禽致病性的方式是独立的和添加剂与NS 3 -249突变。此外，发现NS 1 -2B残基在禽类细胞中生长时改变温度敏感性。西尼罗河病毒（WNV）是一种蚊媒病毒，已在世界许多地区引起人类爆发。鸟类是西尼罗河病毒的自然宿主。然而，不同的西尼罗河病毒株在鸟类中引起不同的疾病结果。在这里，我们比较了两种西尼罗河病毒株，其中一种导致更高的死亡率，并产生更多的病毒在美国乌鸦比其他。先前的研究表明，这种差异在很大程度上是由于两种菌株在NS 3基因中单个氨基酸的差异;然而，这种差异并不能完全解释观察到的效果。在这里，我们发现病毒基因组的另一个区域也影响美国乌鸦的疾病结果，并改变了病毒在鸟类细胞中生长时对温度的敏感性。这些发现有助于我们了解影响WNV感染及其自然宿主疾病结果的遗传特征。在西尼罗河病毒和相关病毒的新菌株中检测到这些特征可能有助于了解和预测未来的爆发。
West Nile virus (WNV) replicates in a wide variety of avian species, which serve as reservoir and amplification hosts. WNV strains isolated in North America, such as the prototype strain NY99, elicit a highly pathogenic response in certain avian species, notably American crows (AMCRs; Corvus brachyrhynchos). In contrast, a closely related strain, KN3829, isolated in Kenya, exhibits a low viremic response with limited mortality in AMCRs. Previous work has associated the difference in pathogenicity primarily with a single amino acid mutation at position 249 in the helicase domain of the NS3 protein. The NY99 strain encodes a proline residue at this position, while KN3829 encodes a threonine. Introduction of an NS3-T249P mutation in the KN3829 genetic background significantly increased virulence and mortality; however, peak viremia and mortality were lower than those of NY99. In order to elucidate the viral genetic basis for phenotype variations exclusive of the NS3-249 polymorphism, chimeric NY99/KN3829 viruses were created. We show herein that differences in the NS1-2B region contribute to avian pathogenicity in a manner that is independent of and additive with the NS3-249 mutation. Additionally, NS1-2B residues were found to alter temperature sensitivity when grown in avian cells. West Nile virus (WNV) is a mosquito-borne virus that has caused outbreaks in humans in many regions of the world. Birds are the natural hosts for WNV. However, different strains of WNV cause different disease outcomes in birds. Here, we compared two WNV strains, one of which causes higher mortality and generates more virus in American crows than the other. Previous research has shown that this difference is due in large part to a difference between the two strains at a single amino acid in the NS3 gene; however, this difference does not completely explain the observed effect. Here we show that another region of the viral genome also affects disease outcomes in American crows, and changes the sensitivity of the virus to temperature when grown in bird cells. These findings help us to understand the genetic features that affect WNV infection and disease outcomes in its natural host. Detection of such features in new strains of WNV and related viruses could help to understand and predict future outbreaks.