西尼罗河病毒感染不会在啮齿动物细胞中诱导 PKR 的激活。
West Nile virus infection does not induce PKR activation in rodent cells.
机构信息
Department of Biology, Georgia State University, Atlanta, GA 30303, USA.
出版信息
Virology. 2011 Dec 5;421(1):51-60. doi: 10.1016/j.virol.2011.08.008. Epub 2011 Oct 7.
Abstract
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.
摘要
双链 RNA 激活的蛋白激酶（PKR）可被病毒双链 RNA 激活，并使真核起始因子 2α磷酸化，从而减少宿主和病毒 mRNA 的翻译。尽管嵌合西尼罗河病毒（WNV）的感染能有效地诱导 PKR 和 eIF2a 的磷酸化，但天然谱系 1 或 2 株的感染却不能。抑制机制的研究表明，在所测试的细胞 PKR 抑制剂蛋白中，只有 Nck，已知与失活的 PKR 相互作用，与 WNV 感染细胞中的 PKR 共定位并共免疫沉淀，而感染 Nck1,2-/-细胞中的 PKR 磷酸化并未增加。几种 WNV 茎环 RNA 可有效地在体外激活 PKR，但不能在感染细胞中激活。WNV 感染不干扰细胞内聚肌苷酸（poly(I:C)）激活的 PKR，且对照和 PKR-/-细胞产生的病毒产量相似。结果表明，WNV 感染细胞中 PKR 磷酸化不是被主动抑制的，但病毒 dsRNA 不能在感染细胞中激活 PKR。
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1
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J Virol. 2010 Oct;84(20):10438-47. doi: 10.1128/JVI.00986-10. Epub 2010 Aug 4.
2
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J Virol. 2010 Aug;84(16):8332-41. doi: 10.1128/JVI.02199-09. Epub 2010 Jun 9.
3
Hepatitis C virus controls interferon production through PKR activation.丙型肝炎病毒通过 PKR 的激活来控制干扰素的产生。
PLoS One. 2010 May 11;5(5):e10575. doi: 10.1371/journal.pone.0010575.
4
Translation initiation of viral mRNAs.病毒 mRNAs 的翻译起始。
Rev Med Virol. 2010 May;20(3):177-95. doi: 10.1002/rmv.649.
5
Ultra-structural localisation of hepatocellular PKR protein using immuno-gold labelling in chronic hepatitis C virus disease.应用免疫胶体金标记技术对慢性丙型肝炎病毒感染患者肝组织 PKR 的超微结构定位
J Mol Histol. 2009 Jun;40(3):171-6. doi: 10.1007/s10735-009-9227-0. Epub 2009 Jul 30.
6
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J Virol. 2009 Oct;83(19):9970-82. doi: 10.1128/JVI.01113-09. Epub 2009 Jul 15.
7
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Antiviral Res. 2009 Sep;83(3):228-37. doi: 10.1016/j.antiviral.2009.05.004. Epub 2009 May 23.
8
Composition and three-dimensional architecture of the dengue virus replication and assembly sites.登革病毒复制与装配位点的组成及三维结构
Cell Host Microbe. 2009 Apr 23;5(4):365-75. doi: 10.1016/j.chom.2009.03.007.
9
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Cell Host Microbe. 2008 Dec 11;4(6):579-91. doi: 10.1016/j.chom.2008.10.007.
10
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