West Nile virus infection does not induce PKR activation in rodent cells.

West Nile virus infection does not induce PKR activation in rodent cells.
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DOI:
10.1016/j.virol.2011.08.008
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发表时间:
2011-12-05
期刊:
影响因子:
3.7
通讯作者:
Brinton MA
Brinton MA
中科院分区:
医学3区
文献类型:
--
作者:
Elbahesh H;Scherbik SV;Brinton MA

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dsRNA激活的蛋白激酶(PKR)被病毒dsRNA激活并磷酸化eIF 2a,从而减少宿主和病毒mRNA的翻译。虽然感染嵌合西尼罗河病毒(WNV)有效地诱导PKR和eIF 2a磷酸化,感染自然谱系1或2株没有。对抑制机制的研究表明,在测试的细胞PKR抑制剂蛋白中,只有已知与失活PKR相互作用的Nck与WNV感染的细胞中的PKR共定位和共免疫沉淀,并且PKR磷酸化在感染的Nck 1,2−/−细胞中没有增加。几种WNV茎环RNA在体外有效激活PKR,但在感染的细胞中不激活。WNV感染不干扰poly(I:C)对细胞内PKR的激活,对照和PKR−/−细胞产生了类似的病毒产量。结果表明,PKR磷酸化在WNV感染的细胞中没有被主动抑制,但PKR在感染的细胞中没有被病毒dsRNA激活。
dsRNA-activated protein kinase (PKR) is activated by viral dsRNAs and phosphorylates eIF2a reducing translation of host and viral mRNA. Although infection with a chimeric West Nile virus (WNV) efficiently induced PKR and eIF2a phosphorylation, infections with natural lineage 1 or 2 strains did not. Investigation of the mechanism of suppression showed that among the cellular PKR inhibitor proteins tested, only Nck, known to interact with inactive PKR, colocalized and co-immunoprecipitated with PKR in WNV-infected cells and PKR phosphorylation did not increase in infected Nck1,2−/− cells. Several WNV stem-loop RNAs efficiently activated PKR in vitro but not in infected cells. WNV infection did not interfere with intracellular PKR activation by poly(I:C) and similar virus yields were produced by control and PKR−/− cells. The results indicate that PKR phosphorylation is not actively suppressed in WNV-infected cells but that PKR is not activated by the viral dsRNA in infected cells.
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