Department of Biology, Georgia State University, Atlanta, Georgia, USA.
J Virol. 2012 Apr;86(7):3647-57. doi: 10.1128/JVI.06549-11. Epub 2012 Jan 18.
West Nile virus (WNV) recently became endemic in the United States and is a significant cause of human morbidity and mortality. Natural WNV strain infections do not induce stress granules (SGs), while W956IC (a lineage 2/1 chimeric WNV infectious clone) virus infections produce high levels of early viral RNA and efficiently induce SGs through protein kinase R (PKR) activation. Additional WNV chimeric viruses made by replacing one or more W956IC genes with the lineage 1 Eg101 equivalent in the W956IC backbone were analyzed. The Eg-NS4b+5, Eg-NS1+3+4a, and Eg-NS1+4b+5 chimeras produced low levels of viral RNA at early times of infection and inefficiently induced SGs, suggesting the possibility that interactions between viral nonstructural proteins and/or between viral nonstructural proteins and cell proteins are involved in suppressing early viral RNA synthesis and membrane remodeling during natural WNV strain infections. Detection of exposed viral double-stranded RNA (dsRNA) in W956IC-infected cells suggested that the enhanced early viral RNA synthesis surpassed the available virus-induced membrane protection and allowed viral dsRNA to activate PKR.
西尼罗河病毒（WNV）最近在美国流行，是导致人类发病率和死亡率的重要原因。天然 WNV 株感染不会诱导应激颗粒（SGs），而 W956IC（一种 2/1 谱系嵌合 WNV 感染性克隆）病毒感染会产生高水平的早期病毒 RNA，并通过蛋白激酶 R（PKR）激活有效地诱导 SGs。通过用 W956IC 骨架中的 1 型 Eg101 等效物替换一个或多个 W956IC 基因来分析其他 WNV 嵌合病毒。Eg-NS4b+5、Eg-NS1+3+4a 和 Eg-NS1+4b+5 嵌合体在感染早期产生低水平的病毒 RNA，并且不能有效地诱导 SGs，这表明病毒非结构蛋白之间的相互作用和/或病毒非结构蛋白与细胞蛋白之间的相互作用可能参与抑制天然 WNV 株感染期间的早期病毒 RNA 合成和膜重塑。在 W956IC 感染的细胞中检测到暴露的病毒双链 RNA（dsRNA）表明，增强的早期病毒 RNA 合成超过了可用的病毒诱导的膜保护，并允许病毒 dsRNA 激活 PKR。
