Ras-丝裂原活化蛋白激酶信号通路对乙型肝炎病毒复制的调控
Regulation of hepatitis B virus replication by the ras-mitogen-activated protein kinase signaling pathway.
作者信息
Zheng Yanyan, Li Jie, Johnson Deborah L, Ou Jing-hsiung
机构信息
Department of Molecular Microbiology and Immunology, Keck School of Medicine, University of Southern California, 2011 Zonal Avenue, Los Angeles, CA 90033, USA.
出版信息
J Virol. 2003 Jul;77(14):7707-12. doi: 10.1128/jvi.77.14.7707-7712.2003.
The replication of hepatitis B virus (HBV) can be regulated by a variety of factors, including hormones, growth factors, and cytokines. However, the molecular mechanisms of these regulations are largely unknown. Ras is a small GTPase that responds to many of these external stimuli. In this study, we investigated the possible effect of Ras on the replication of HBV. Our results indicated that activated Ras could suppress the replication of HBV in both Huh7 and HepG2 cells. This suppression was independent of the X protein and most likely occurred at the transcriptional level. Deletion-mapping analysis of the HBV core promoter and its upstream ENI and ENII enhancers revealed multiple elements responsive to activated Ras. This suppression of HBV replication by activated Ras was apparently mediated by the mitogen-activated protein (MAP) kinase pathway, as it was accompanied by activation of ERK1/2 and abolished by the MEK1/2 inhibitor U0126. Our results thus indicate that external stimuli may suppress HBV replication through the Ras-MAP kinase pathway.
乙型肝炎病毒（HBV）的复制可受多种因素调控，包括激素、生长因子和细胞因子。然而，这些调控的分子机制大多尚不清楚。Ras是一种小GTP酶，可对许多此类外部刺激作出反应。在本研究中，我们调查了Ras对HBV复制可能产生的影响。我们的结果表明，活化的Ras可抑制Huh7和HepG2细胞中HBV的复制。这种抑制与X蛋白无关，最有可能发生在转录水平。对HBV核心启动子及其上游ENI和ENII增强子的缺失定位分析揭示了多个对活化Ras有反应的元件。活化的Ras对HBV复制的这种抑制显然是由丝裂原活化蛋白（MAP）激酶途径介导的，因为它伴随着ERK1/2的激活，并被MEK1/2抑制剂U0126所消除。因此，我们的结果表明，外部刺激可能通过Ras-MAP激酶途径抑制HBV复制。
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