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首页> 外文期刊>Proceedings of the National Academy of Sciences of the United States of America >Unique antiviral mechanism discovered in anti-hepatitis B virus research with a natural product analogue
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Unique antiviral mechanism discovered in anti-hepatitis B virus research with a natural product analogue

机译：在抗乙型肝炎病毒研究中使用天然产物类似物发现的独特抗病毒机制

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摘要

Helioxanthin is a natural product that inhibits the replication of a number of viruses. We found that a previously undescribed helioxanthin analogue, 8-1, exhibited potent anti-hepatitis B virus (HBV) activity with little cytotoxicity. 8-1 suppressed both HBV RNA and protein expression, as well as DNA replication of both wild-type and 3TC-resistant virus. Time-course analyses revealed that RNA expression was blocked first after treatment with 8-1, followed by viral proteins, and then DNA. 8-1 inhibited the activity of all HBV promoters by decreasing the binding of hepatocyte nuclear factor 4 (HNF-4), HNF-3, and fetoprotein factor to the precore/core promoter enhancer II region. The amount of HNF-4 and HNF-3 was decreased posttranscriptionally by 8-1 in HBV-producing cells, but not in HBV-negative cells. Therefore, 8-1 suppresses HBV replication by posttranscriptional down-regulation of critical transcription factors in HBV-producing cells, thus diminishing HBV promoter activity and blocking viral gene expression and replication. This mechanism is unique and different from other anti-HBV compounds previously described.
机译：Helioxanthin是一种天然产物，可抑制多种病毒的复制。我们发现以前未描述的氧黄素类似物8-1表现出有效的抗乙型肝炎病毒（HBV）活性，几乎没有细胞毒性。 8-1抑制了HBV RNA和蛋白质表达，以及野生型和3TC耐药病毒的DNA复制。时程分析表明，RNA的表达在用8-1处理后首先被阻断，随后是病毒蛋白，然后是DNA。 8-1通过减少肝细胞核因子4（HNF-4），HNF-3和胎蛋白因子与前核心/核心启动子增强子II区域的结合来抑制所有HBV启动子的活性。在产生HBV的细胞中，转录后HNF-4和HNF-3的量减少了8-1，而在HBV阴性细胞中则没有。因此，8-1通过转录后下调生产HBV的细胞中的关键转录因子来抑制HBV复制，从而降低HBV启动子活性并阻断病毒基因的表达和复制。该机制是独特的，并且与先前所述的其他抗HBV化合物不同。

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