Interferon inhibits dengue virus infection by preventing translation of viral RNA through a PKR-independent mechanism
Interferon inhibits dengue virus infection by preventing translation of viral RNA through a PKR-independent mechanism
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DOI：
10.1006/viro.2001.1114
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发表时间：
2001-10-25
期刊：
影响因子：
3.7
通讯作者：
Harris, E
中科院分区：
文献类型：
--
作者：
Diamond, MS;Harris, E
先前，我们证明了用干扰素(IFN) α + γ或β + γ预处理细胞可以抑制登革热病毒（DV）的复制。在本研究中，我们通过实验来更好地确定IFN阻断登革热病毒（DV） RNA积累的机制。用干扰素β + γ预处理人肝癌细胞并没有显著改变病毒附着、病毒进入或核衣壳渗入细胞质。即使将裸DV RNA直接转染到细胞中，IFN的抑制作用仍然存在，这证实了与病毒进入相关的步骤不是IFN作用的主要目标。生物合成标记实验表明，IFN消除了在RNA复制之前发生的传染性病毒RNA的翻译。亚细胞分离实验表明，干扰素没有显著改变病毒RNA附着在核糖体上的能力。IFN的抗病毒作用似乎与IFN诱导的双链rna激活蛋白激酶（PKR）和RNase L无关，因为基因缺陷的PKR- RNase L-细胞被DV感染后对IFN的抑制保持敏感性。我们得出结论，IFN通过一种新的、不依赖于pcr的机制，通过抑制传染性病毒RNA的翻译来预防DV感染。(C) 2001学术出版社。
Previously, we demonstrated that pretreatment of cells with interferon (IFN) alpha + gamma or beta + gamma inhibited dengue virus (DV) replication. In this study, experiments were per-formed to better define the mechanism by which IFN blocks the accumulation of dengue virus (DV) RNA. Pretreatment of human hepatoma cells with IFN beta + gamma did not significantly alter virus attachment, viral entry, or nucleocapsid penetration into the cytoplasm. The inhibitory effect of IFN was retained even when naked DV RNA was transfected directly into cells, confirming that steps associated with viral entry were not the primary target of IFN action. Biosynthetic labeling experiments revealed that IFN abolished the translation of Infectious viral RNA that occurred prior to RNA replication. Subcellular fractionation experiments demonstrated that IFN did not significantly alter the ability of viral RNA to attach to ribosomes. The antiviral effect of IFN appeared independent of the IFN-Induced, double-stranded RNA-activated protein kinase (PKR) and RNase L, as genetically deficient PKR- RNase L- cells that were infected by DV retained sensitivity to Inhibition by IFN.. We conclude that IFN prevents DV infection by inhibiting translation of the Infectious viral RNA through a novel, PKR-independent mechanism. (C) 2001 Academic Press.