Comprehensive proteomic analysis of host cell lipid rafts modified by HBV infection
Comprehensive proteomic analysis of host cell lipid rafts modified by HBV infection
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乙型肝炎病毒感染修饰的宿主细胞脂筏的综合蛋白质组学分析
DOI：
10.1016/j.jprot.2011.09.011
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发表时间：
2012-01-04
影响因子：
3.3
通讯作者：
Huang, Canhua
中科院分区：
文献类型：
--
作者：
Xie, Na;Huang, Kai;Huang, Canhua
脂筏是富含胆固醇和鞘脂的膜微结构域，已被证明参与各种病毒的进入、组装和出芽。然而，它们参与HBV复制的特征仍然很少。在一项初步研究中，我们观察到甲基- β -环糊精介导的脂筏中胆固醇的消耗可以明显损害HBV的释放，并且这种影响可以通过补充外源性胆固醇来逆转，这表明脂筏在HBV生命周期中起重要作用。为了进一步了解HBV是如何利用宿主细胞脂筏来促进复制的，我们采用了综合蛋白质组学方法，利用2DE-MS/MS结合基于silac的定量蛋白质组学，分析了宿主细胞脂筏在HBV感染后的蛋白质组变化。使用这些方法，共鉴定了97个差异表达蛋白。生物信息学分析表明，HBV感染过程涉及多种宿主细胞途径，包括信号转导、代谢、免疫应答、转运、囊泡运输、细胞粘附和细胞离子稳态。这些数据将为进一步研究HBV的发病机制提供有价值的线索。爱思唯尔B.V.版权所有
Lipid rafts are cholesterol- and sphingolipid-rich membrane microdomains that have been shown to participate in the entry, assembly and budding of various viruses. However, their involvement in HBV replication remains poorly characterized. In a preliminary study, we observed that HBV release could be markedly impaired by methyl-beta-cyclodextrin mediated depletion of cholesterol in lipid rafts, and that this effect could be reversed by replenishment of exogenous cholesterol, suggesting that lipid rafts play an important role in the HBV life cycle. To further understanding how HBV exploited host cell lipid rafts to benefit replication, comprehensive proteomic approaches were used to profile the proteome changes of host cell lipid rafts in response to HBV infection using 2DE-MS/MS, in combination with SILAC-based quantitative proteomics. Using these approaches, a total of 97 differentially expressed proteins were identified. Bioinforrnatics analysis suggested that multiple host cell pathways were involved in the HBV infection processes including signal transduction, metabolism, immune response, transport, vesicle trafficking, cell adhesion and cellular ion homeostasis. These data will provide valuable clues for further investigation of HBV pathogenesis. Crown Copyright (C) 2011 Published by Elsevier B.V. All rights reserved.