A broad investigation of the HBV-mediated changes to primary hepatocyte physiology reveals HBV significantly alters metabolic pathways.
A broad investigation of the HBV-mediated changes to primary hepatocyte physiology reveals HBV significantly alters metabolic pathways.
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DOI：
10.1016/j.metabol.2018.01.007
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发表时间：
2018-06
期刊：
影响因子：
--
通讯作者：
Bouchard MJ
中科院分区：
文献类型：
--
作者：
Lamontagne RJ;Casciano JC;Bouchard MJ
作为肝癌发展的主要危险因素，B肝炎病毒（HBV）的慢性感染是一个重大的全球健康问题。尽管存在有效的HBV疫苗，但全世界至少有2.4亿人慢性感染HBV。治疗慢性HBV的治疗选择仍然有限，没有一种可以达到绝对治愈。为了开发新的治疗靶点，需要更好地了解病毒-宿主相互作用的复杂网络。由于肝脏的中心代谢作用，我们评估了HBV感染的代谢影响，以确定病毒依赖性因素和代谢途径，这些因素和代谢途径可作为治疗干预的新点。用对照腺病毒、表达HBV基因组的大于单位长度拷贝的腺病毒或表达HBV ×蛋白（HBx）的腺病毒感染原代大鼠肝细胞。在感染后24和48小时，分析了一组369种代谢物的HBV或HBx诱导的变化。通路分析用于确定在HBV或HBx表达存在下改变的关键代谢通路，并且这些发现通过整合药物学上可用的基因表达数据得到进一步支持。我们观察到在HBV复制或HBx表达的背景下多种代谢物的明显变化。有趣的是，HBV和HBx在两个时间点均改变了一组7种代谢物（麦芽三糖、麦芽糖、肉豆蔻酸[14：0]、花生酸[20：0]、3-羟基丁酸[BHBA]、肌醇和2-棕榈酰甘油[16：0]）。此外，从转录组为基础的数据集的数据整合使我们能够确定代谢途径，包括长链脂肪酸代谢，糖酵解和糖原代谢，这是显着改变HBV和HBx。由于肝脏是代谢过程的中心调节器，因此了解HBV复制和HBV蛋白表达如何影响肝细胞的代谢功能非常重要。通过分析广泛的代谢物，我们研究了这种代谢影响。这些研究的结果已经确定了HBV感染肝细胞的代谢后果，并将有助于为新的研究方向奠定基础，并可能开发新的抗HBV治疗药物。
As the leading risk factor for the development of liver cancer, chronic infection with hepatitis B virus (HBV) represents a significant global health concern. Although an effective HBV vaccine exists, at least 240 million people are chronically infected with HBV worldwide. Therapeutic options for the treatment of chronic HBV remain limited, and none achieve an absolute cure. To develop novel therapeutic targets, a better understanding of the complex network of virus-host interactions is needed. Because of the central metabolic role of the liver, we assessed the metabolic impact of HBV infection as a means to identify viral dependency factors and metabolic pathways that could serve as novel points of therapeutic intervention. Primary rat hepatocytes were infected with a control adenovirus, an adenovirus expressing a greater-than-unit-length copy of the HBV genome, or an adenovirus expressing the HBV × protein (HBx). A panel of 369 metabolites was analyzed for HBV- or HBx-induced changes 24 and 48 hours post infection. Pathway analysis was used to identify key metabolic pathways altered in the presence of HBV or HBx expression, and these findings were further supported through integration of publically available gene expression data. We observed distinct changes to multiple metabolites in the context of HBV replication or HBx expression. Interestingly, a panel of 7 metabolites (maltotriose, maltose, myristate [14:0], arachidate [20:0], 3-hydroxybutyrate [BHBA], myo-inositol, and 2-palmitoylglycerol [16:0]) were altered by both HBV and HBx at both time points. In addition, incorporation of data from a transcriptome-based dataset allowed us to identify metabolic pathways, including long chain fatty acid metabolism, glycolysis, and glycogen metabolism, that were significantly altered by HBV and HBx. Because the liver is a central regulator of metabolic processes, it is important to understand how HBV replication and HBV protein expression affects the metabolic function of hepatocytes. Through analysis of a broad panel of metabolites we investigated this metabolic impact. The results of these studies have defined metabolic consequences of an HBV infection of hepatocytes and will help to lay the groundwork for novel research directions and, potentially, development of novel anti-HBV therapeutics.
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影响因子：
29.4
作者：
El-Serag HB
通讯作者：
El-Serag HB
DOI：
10.1074/jbc.m111.259978
发表时间：
2011-08-26
期刊：
The Journal of biological chemistry
影响因子：
--
作者：
Shin HJ;Park YH;Kim SU;Moon HB;Park DS;Han YH;Lee CH;Lee DS;Song IS;Lee DH;Kim M;Kim NS;Kim DG;Kim JM;Kim SK;Kim YN;Kim SS;Choi CS;Kim YB;Yu DY
通讯作者：
Yu DY
影响因子：
6.7
作者：
Lamontagne J;Mell JC;Bouchard MJ
通讯作者：
Bouchard MJ
WGCNA：用于加权相关网络分析的 R 包。
影响因子：
3
作者：
Langfelder P;Horvath S
通讯作者：
Horvath S
基于RNA-SEQ的转录组分析乙型肝炎病毒（HEV）和丙型肝炎病毒（HBV）复制子转染了HUH-7细胞。
影响因子：
3.7
作者：
Jagya N;Varma SP;Thakral D;Joshi P;Durgapal H;Panda SK
通讯作者：
Panda SK