Expression of hepatitis C virus core protein impairs DNA repair in human hepatoma cells
Expression of hepatitis C virus core protein impairs DNA repair in human hepatoma cells
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DOI：
10.1016/j.canlet.2003.11.035
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发表时间：
2004-06-25
期刊：
影响因子：
9.7
通讯作者：
Fevery, J
中科院分区：
文献类型：
--
作者：
van Pelt, JF;Severi, T;Fevery, J
多项研究已证明丙型肝炎病毒（HCV）感染与肝细胞癌之间存在重要联系。其机制尚不清楚，可能与病毒蛋白有关。我们研究了HCV核心蛋白对紫外线诱导的DNA损伤后DNA修复的影响。因此，我们开发并表征了稳定转染的HepG2细胞系，其表达HCV核心蛋白，如免疫组织化学所示。这些细胞修复DNA损伤的能力明显低于对照细胞。HCV核心蛋白对DNA修复的抑制使细胞对获得突变更敏感，与感染肝脏中增强的体内细胞周转相结合，可能会增加HCV感染细胞因其他病毒因素或暴露于环境因素（食物、药物、吸烟、酒精等）而恶性转化的可能性。有趣的是，全长HCV核心的表达确实增加了我们开发的一种细胞系中的细胞倍增时间，这不能归因于这些细胞中细胞凋亡的增加或端粒酶活性的变化。(C)2003 Elsevier Ltd.保留所有权利。
Several studies have documented the important association between hepatitis C virus (HCV) infection and hepatocellular carcinoma. The mechanisms involved are still unknown and could involve viral proteins. We investigated the effect of HCV-core protein on DNA repair after UV-induced DNA damage. Therefore, we developed and characterized stably transfected HepG2 cell lines that express HCV-core protein as demonstrated by immunohistochemistry. These cells were significantly less capable to repair the DNA damage than control cells. This suppression of DNA repair by HCV-core protein renders the cells more sensitive to acquire mutations that in combination with enhanced in vivo cell turnover in the infected liver might increase the likelihood of malignant transformation of HCV-infected cells by other viral factors or upon exposure to environmental factors (food, drugs, smoking, alcohol, etc.). Interestingly, expression of the full-length HCV core did increase the cell doubling time in one of the cell lines we had developed that could not be attributed to an increase in apoptosis or change in telomerase activity in these cells. (C) 2003 Elsevier Ltd. All rights reserved.