Siavoshian S, Abraham J D, Kieny M P, Schuster C
INSERM U544, Strasbourg, France.
Arch Virol. 2004 Feb;149(2):323-36. doi: 10.1007/s00705-003-0205-7. Epub 2003 Sep 22.
Several reports have shown that activity and/or expression of p53 can be modulated by Hepatitis C virus (HCV) proteins and may interfere with normal regulation of cell growth. In order to understand the relationship between p53 function and HCV proteins expression, we have investigated potential effects of the core, NS3, NS5A and NS5B proteins on Huh-7 (p53 +/+) and Hep3B (p53 -/-) cell proliferation. The effect of HCV proteins transiently expressed after recombinant-adenoviral infection was analyzed by Western blot, crystal violet and propidium iodide staining. Expression of the core, NS3, NS5A or NS5B proteins inhibited cell proliferation and blocked both cell lines in the G2/M phase of the cell cycle. c-myc and p53 expression were respectively induced and increased in Huh-7 cells only following expression of the Core protein. No expression of p21(waf1/cip1) could be detected and expression of cyclin A, cdk2 and p27(Kip1) were independent of HCV protein's expression. Our results show that the effect of core, NS3, NS5A and NS5B on cell proliferation is independent of p53 expression and that only the Core protein, induces the expression of both c-myc and p53.
多项报告显示，丙型肝炎病毒（HCV）蛋白可调节p53的活性和/或表达，并可能干扰细胞生长的正常调节。为了了解p53功能与HCV蛋白表达之间的关系，我们研究了核心蛋白、NS3、NS5A和NS5B蛋白对Huh-7（p53 +/+）和Hep3B（p53 -/-）细胞增殖的潜在影响。通过蛋白质免疫印迹法、结晶紫染色和碘化丙啶染色分析重组腺病毒感染后瞬时表达的HCV蛋白的作用。核心蛋白、NS3、NS5A或NS5B蛋白的表达抑制细胞增殖，并使两种细胞系均停滞在细胞周期的G2/M期。仅在核心蛋白表达后，Huh-7细胞中的c-myc和p53表达分别被诱导并增加。未检测到p21（waf1/cip1）的表达，细胞周期蛋白A、细胞周期蛋白依赖性激酶2（cdk2）和p27（Kip1）的表达与HCV蛋白的表达无关。我们的结果表明，核心蛋白、NS3、NS5A和NS5B对细胞增殖的影响与p53表达无关，只有核心蛋白诱导c-myc和p53的表达。
