Escape from Transcriptional Shutoff during Poliovirus Infection: NF-κB-Responsive Genes IκBa and A20
Escape from Transcriptional Shutoff during Poliovirus Infection: NF-κB-Responsive Genes IκBa and A20
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DOI：
10.1128/jvi.00575-11
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发表时间：
2011-10-01
影响因子：
5.4
通讯作者：
Sarnow, Peter
中科院分区：
文献类型：
--
作者：
Doukas, Tammy;Sarnow, Peter
长期以来，人们已经知道，脊髓灰质炎病毒感染培养细胞会导致大多数宿主基因转录的总体抑制。我们研究了在病毒感染过程中，通过硫尿苷标记新合成的宿主mRNA，所选择的宿主基因是否可以逃脱转录抑制。使用cDNA微阵列杂交从硫醇化的mRNA的cDNA，一个小的主机转录本集进行了鉴定，并通过定量PCR和北方和Western印迹分析验证其表达。这些转录本是由在其启动子区显示富集NF-κ B B结合位点的基因合成的，这表明一些NF-κ B调节的启动子可以逃避病毒诱导的转录抑制。特别是，NF-κ B的两个负调节因子I κ Ba和A20在病毒感染期间上调。A20的耗尽增强了病毒RNA丰度和病毒产量，认为细胞通过抵消NF-κ B诱导的前病毒效应来响应病毒感染。
It has been known for a long time that infection of cultured cells with poliovirus results in the overall inhibition of transcription of most host genes. We examined whether selected host genes can escape transcriptional inhibition by thiouridine marking newly synthesized host mRNAs during viral infection. Using cDNA microarrays hybridized to cDNAs made from thiolated mRNAs, a small set of host transcripts was identified and their expression verified by quantitative PCR and Northern and Western blot analyses. These transcripts were synthesized from genes that displayed enrichment for NF-kappa B binding sites in their promoter regions, suggesting that some NF-kappa B-regulated promoters can escape the virus-induced inhibition of transcription. In particular, two negative regulators of NF-kappa B, I kappa Ba and A20, were upregulated during viral infection. Depletion of A20 enhanced viral RNA abundance and viral yield, arguing that cells respond to virus infection by counteracting NF-kappa B-induced proviral effects.