Oxford Glycobiology Institute, Department of Biochemistry, University of Oxford, Oxford, UK.
Hepatology. 2010 Aug;52(2):443-53. doi: 10.1002/hep.23733.
Hepatitis C virus (HCV) is a major cause of liver disease but the full impact of HCV infection on the hepatocyte is poorly understood. RNA sequencing (RNA-Seq) is a novel method to analyze the full transcriptional activity of a cell or tissue, thus allowing new insight into the impact of HCV infection. We conducted the first full-genome RNA-Seq analysis in a host cell to analyze infected and noninfected cells, and compared this to microarray and proteomic analyses. The combined power of the triple approach revealed that HCV infection affects a number of previously unreported canonical pathways and biological functions, including pregnane X receptor/retinoic acid receptor activation as a potential host antiviral response, and integrin-linked kinase signaling as an entry factor. This approach also identified several mechanisms implicated in HCV pathogenesis, including an increase in reactive oxygen species. HCV infection had a broad effect on cellular metabolism, leading to increases in cellular cholesterol and free fatty acid levels, associated with a profound and specific decrease in cellular glucose levels.
RNA-Seq technology, especially when combined with established methods, demonstrated that HCV infection has potentially wide-ranging effects on cellular gene and protein expression. This in vitro study indicates a substantial metabolic impact of HCV infection and highlights new mechanisms of virus-host interaction which may be highly relevant to pathogenesis in vivo.
丙型肝炎病毒（HCV）是肝脏疾病的主要病因，但人们对 HCV 感染对肝细胞的全面影响仍知之甚少。RNA 测序（RNA-Seq）是一种分析细胞或组织全部转录活性的新方法，从而能够深入了解 HCV 感染的影响。我们首次在宿主细胞中进行了全基因组 RNA-Seq 分析，以比较感染和未感染的细胞，并将其与微阵列和蛋白质组学分析进行比较。这三种方法的综合作用表明，HCV 感染会影响许多以前未报道的经典途径和生物学功能，包括作为潜在宿主抗病毒反应的孕烷 X 受体/维甲酸受体激活，以及整合素连接激酶信号传导作为进入因素。这种方法还确定了几种与 HCV 发病机制有关的机制，包括活性氧物质的增加。HCV 感染对细胞代谢有广泛影响，导致细胞胆固醇和游离脂肪酸水平升高，同时细胞葡萄糖水平显著且特异性降低。
RNA-Seq 技术，尤其是与已建立的方法相结合，表明 HCV 感染对细胞基因和蛋白质表达可能有广泛的影响。这项体外研究表明 HCV 感染对代谢有重大影响，并强调了病毒-宿主相互作用的新机制，这些机制可能与体内发病机制高度相关。
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