Transcriptional regulation of hepatitis B virus by nuclear hormone receptors is a critical determinant of viral tropism.

Transcriptional regulation of hepatitis B virus by nuclear hormone receptors is a critical determinant of viral tropism.
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DOI:
10.1073/pnas.98.4.1841
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发表时间:
2001-02
影响因子:
11.1
通讯作者:
Hong Tang;Alan McLachlan
Hong Tang;Alan McLachlan
中科院分区:
综合性期刊1区
文献类型:
--
作者:
Hong Tang;Alan McLachlan

文献摘要

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向肝性是B型肝炎病毒(HBV)感染的显著特征。非肝来源的细胞系不能独立支持HBV复制。在这里,我们表明,核激素受体,肝细胞核因子4和类维生素A X受体α加上过氧化物酶体增殖物激活受体α,支持HBV复制在非肝细胞通过控制前基因组RNA合成,表明这些肝脏富集的转录因子控制一个独特的分子开关限制病毒的嗜性。相反,肝细胞核因子3拮抗核激素受体介导的病毒复制,表现出不同的调节作用,这些肝脏富集的转录因子。
Hepatotropism is a prominent feature of hepatitis B virus (HBV) infection. Cell lines of nonhepatic origin do not independently support HBV replication. Here, we show that the nuclear hormone receptors, hepatocyte nuclear factor 4 and retinoid X receptor alpha plus peroxisome proliferator-activated receptor alpha, support HBV replication in nonhepatic cells by controlling pregenomic RNA synthesis, indicating these liver-enriched transcription factors control a unique molecular switch restricting viral tropism. In contrast, hepatocyte nuclear factor 3 antagonizes nuclear hormone receptor-mediated viral replication, demonstrating distinct regulatory roles for these liver-enriched transcription factors.