RNA-sequencing analysis of 5' capped RNAs identifies many new differentially expressed genes in acute hepatitis C virus infection.
RNA-sequencing analysis of 5' capped RNAs identifies many new differentially expressed genes in acute hepatitis C virus infection.
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DOI：
10.3390/v4040581
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发表时间：
2012-04
期刊：
影响因子：
--
通讯作者：
Hagedorn CH
中科院分区：
文献类型：
--
作者：
Papic N;Maxwell CI;Delker DA;Liu S;Heale BS;Hagedorn CH
我们首次报道了从急性丙型肝炎病毒（HCV）感染的Huh 7.5细胞中分离的5' cap (Pol II) RNA的RNA测序，这为鉴定参与病毒-宿主相互作用的差异表达的带注释和未带注释的基因提供了一种通用方法。在急性感染的增殖性Huh 7.5细胞中，我们分别在6、48和72小时鉴定出100,684和1,844个显著差异表达的注释基因（倍数变化≥1.5，Bonferroni校正p值< 0.05）。大多数差异表达基因（>80%）和生物学途径（如脂肪细胞因子、Notch、Hedgehog和nod样受体信号）未被先前的基因阵列研究发现。这些基因是宿主免疫、炎症和致癌途径的关键组成部分，并提供了有关可能有利于病毒或介导HCV诱导病理的变化的新信息。新发现的高度上调的FUT1和KLHDC7B基因的RNAi敲低研究提供了证据，证明它们的基因产物调节和促进HCV在肝细胞中的复制。我们的方法还发现了新的Pol II无注释转录本上调。结果进一步确定了调节HCV在肝细胞内复制的新途径，并表明我们的方法将在模型系统和临床生物标本中研究病毒-宿主相互作用方面具有普遍应用。
We describe the first report of RNA sequencing of 5' capped (Pol II) RNAs isolated from acutely hepatitis C virus (HCV) infected Huh 7.5 cells that provides a general approach to identifying differentially expressed annotated and unannotated genes that participate in viral-host interactions. We identified 100, 684, and 1,844 significantly differentially expressed annotated genes in acutely infected proliferative Huh 7.5 cells at 6, 48, and 72 hours, respectively (fold change ≥ 1.5 and Bonferroni adjusted p-values < 0.05). Most of the differentially expressed genes (>80%) and biological pathways (such as adipocytokine, Notch, Hedgehog and NOD-like receptor signaling) were not identified by previous gene array studies. These genes are critical components of host immune, inflammatory and oncogenic pathways and provide new information regarding changes that may benefit the virus or mediate HCV induced pathology. RNAi knockdown studies of newly identified highly upregulated FUT1 and KLHDC7B genes provide evidence that their gene products regulate and facilitate HCV replication in hepatocytes. Our approach also identified novel Pol II unannotated transcripts that were upregulated. Results further identify new pathways that regulate HCV replication in hepatocytes and suggest that our approach will have general applications in studying viral-host interactions in model systems and clinical biospecimens.
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