Interaction of TIA-1/TIAR with West Nile and dengue virus products in infected cells interferes with stress granule formation and processing body assembly
Interaction of TIA-1/TIAR with West Nile and dengue virus products in infected cells interferes with stress granule formation and processing body assembly
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DOI：
10.1073/pnas.0703348104
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发表时间：
2007-05-22
影响因子：
11.1
通讯作者：
Brinton, Margo A.
中科院分区：
文献类型：
--
作者：
Emara, Mohamed M.;Brinton, Margo A.
西尼罗河病毒负链3'末端茎环（SO RNA）先前已被证明能特异性结合细胞应激颗粒（SG）成分、T细胞胞内抗原 - 1（TIA - 1）以及相关蛋白TIAR。体外TIAR的结合效率是TIA - 1的10倍。3'（ - ）SL作为基因组RNA合成的启动子发挥作用。在西尼罗河病毒和登革热病毒感染细胞的核周区域观察到TIAR和TIA - 1与病毒复制复合物成分双链RNA（dsRNA）和NS3的共定位。TIAR在核周区域的积累动力学与基因组RNA合成的动力学相似。相反，TIA - 1向核周区域的重新定位仅在RNA合成达到最大水平之后才开始，除非不存在TIAR。病毒感染不会诱导应激颗粒产生，并且随着TIAR的重新定位，对应激颗粒诱导的渐进性抵抗与亚砷酸盐诱导同时出现。在感染细胞中还观察到加工体数量逐渐减少。这些数据表明TIAR与病毒成分的相互作用促进了黄病毒基因组RNA合成并抑制了应激颗粒形成，从而防止宿主翻译的关闭。
The West Nile virus minus-strand 3 ' terminal stem loop (SO RNA was previously shown to bind specifically to cellular stress granule (SG) components, T cell intracellular antigen-1 (TIA-1) and the related protein TIAR. In vitro TIAR binding was 10 times more efficient than TIA-1. The 3 '(-)SL functions as the promoter for genomic RNA synthesis. Colocalization of TIAR and TIA-1 with the viral replication complex components dsRNA and NS3 was observed in the perinuclear regions of West Nile virus- and dengue virus-infected cells. The kinetics of accumulation of TIAR in the perinuclear region was similar to those of genomic RNA synthesis. In contrast, relocation of TIA-1 to the perinuclear region began only after maximal levels of RNA synthesis had been achieved, except when TIAR was absent. Virus infection did not induce SGs and progressive resistance to SG induction by arsenite developed coincident with TIAR relocation. A progressive decrease in the number of processing bodies was secondarily observed in infected cells. These data suggest that the interaction of TIAR with viral components facilitates flavivirus genome RNA synthesis and inhibits SG formation, which prevents the shutoff of host translation.