Yuan Weilan, Huang Tao, Yu Jian, Zeng Lingyao, Lian Baofeng, He Qinwen, Li Yixue, Zhang Xiaoyan, Zhou Fengli, Xie Lu
School of Life Sciences and Technology, Tongji University, Shanghai 200092, PR China; Shanghai Center for Bioinformation Technology, Shanghai 201203, PR China.
Biochim Biophys Acta. 2014 Jan;1844(1 Pt B):271-9. doi: 10.1016/j.bbapap.2013.06.002. Epub 2013 Jun 14.
Previously, the different mechanisms of HBV infection and HCV infection were studied experimentally. Multiple studies also compared the differential network between HBV induced HCC and HCV induced HCC based on gene expression data. However network level comparison combining viral-human interaction network and dysfunctional protein interaction network for HBV and HCV-HCC has rarely been done before. In this work we did some pioneer job in construction of HBV/HCV viral dysfunctional network in HCC, in hope of investigating viral infection impact on the change of genome expression and eventually, the development of HCC. We found that HBx, the main HBV viral protein, directly acted on the gene groups of cell cycle, which could perfectly explain the dominant cell proliferation effect shown in the dysfunctional network of HBV-HCC. On the other hand, multiple important HCV viral proteins including CORE, NS3 and NS5A were found to target very important cancer related proteins such as TP53 and SMAD3, but no direct targeting to major immune response or inflammation related proteins. Therefore the dominant activation of immune response and inflammation related pathways shown in dysfunctional network of HCV-HCC might not be a direct effect of HCV infection. They might have been an indirect demonstration of activated cancer promoting pathways. Similar approaches may as well be applied to other important virus infection caused human diseases to help elucidate the mechanisms of virus-host interaction, and even help with investigations on anti-virus based therapies. This article is part of a Special Issue entitled: Computational Proteomics, Systems Biology & Clinical Implications.
此前，已通过实验研究了HBV感染和HCV感染的不同机制。多项研究还基于基因表达数据比较了HBV诱导的肝癌和HCV诱导的肝癌之间的差异网络。然而，此前很少有人将病毒-人类相互作用网络和功能失调的蛋白质相互作用网络结合起来，对HBV和HCV-HCC进行网络层面的比较。在这项工作中，我们在构建肝癌中的HBV/HCV病毒功能失调网络方面做了一些开拓性工作，希望研究病毒感染对基因组表达变化的影响，并最终研究肝癌的发展。我们发现，HBV的主要病毒蛋白HBx直接作用于细胞周期的基因组，这可以完美地解释HBV-HCC功能失调网络中显示的主要细胞增殖效应。另一方面，发现包括CORE、NS3和NS5A在内的多种重要HCV病毒蛋白靶向非常重要的癌症相关蛋白，如TP53和SMAD3，但没有直接靶向主要的免疫反应或炎症相关蛋白。因此，HCV-HCC功能失调网络中显示的免疫反应和炎症相关途径的主要激活可能不是HCV感染的直接作用。它们可能是激活的促癌途径的间接表现。类似的方法也可以应用于其他重要病毒感染引起的人类疾病，以帮助阐明病毒-宿主相互作用的机制，甚至有助于基于抗病毒的治疗研究。本文是名为：计算蛋白质组学、系统生物学与临床意义的特刊的一部分。
