Interferon-α suppresses hepatitis B virus enhancer II activity via the protein kinase C pathway
Interferon-α suppresses hepatitis B virus enhancer II activity via the protein kinase C pathway
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DOI：
10.1016/j.virol.2012.07.002
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发表时间：
2012-10-25
期刊：
影响因子：
3.7
通讯作者：
Takehara, Tetsuo
中科院分区：
文献类型：
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作者：
Nawa, Takatoshi;Ishida, Hisashi;Takehara, Tetsuo
HBV具有两个增强子（En）区域，每个区域促进其自身的转录。En II比En I更强地调节HBV复制的关键产物前基因组RNA的产生。虽然已发现IFN-α抑制En I活性，但其对En II活性的影响尚未研究。在这里，我们使用荧光素酶测定来证明IFN-α抑制En II活性。用几种缺失/突变构建体的分析鉴定了En II序列内的两个主要区段，nt 1703-1727和nt 1746-1770，作为IFN-α抑制作用的原因。用蛋白激酶C（PKC）抑制剂预处理阻断了这种作用，而不管IFN-α刺激后磷酸化STAT 1和Mx的表达水平如何。这些结果表明IFN-α通过PKC途径抑制En II活性，这可能是HBV复制的另一种抑制途径。(136话）。(C)2012 Elsevier Inc. All rights reserved.
HBV has two enhancer (En) regions each of which promotes its own transcription. En II regulates production of pregenomic RNA, a key product of HBV replication, more strongly than En I. Although IFN-alpha has been found to suppress En I activity, its effect on En II activity has not been examined. Here we used luciferase assay to demonstrate that IFN-alpha suppresses En II activity. Analysis with several deletion/mutation constructs identified two major segments, nt 1703-1727 and nt 1746-1770, within the En II sequence as being responsible for the suppressive effects of IFN-alpha. Pre-treatment with protein kinase C (PKC) inhibitors blocked this effect regardless of the expression levels of phospho-STAT1 and Mx upon IFN-alpha stimulation. These results indicate that IFN-alpha suppresses En II activity via the PKC pathway, which may be an alternative suppressive pathway for HBV replication. (136 words). (C) 2012 Elsevier Inc. All rights reserved.