Tang H, Banks K E, Anderson A L, McLachlan A
Dept. of Cell Biology, Scripps Research Institute, La Jolla, California 92037, USA.
Drug News Perspect. 2001 Aug;14(6):325-34.
Hepatitis B virus (HBV) replicates by the reverse transcription of the 3.5-kb viral pregenomic RNA. Therefore, the regulation of the transcription of the pregenomic RNA is a critical step in the viral life cycle. Various ubiquitous and liver-enriched transcription factors have been shown to modulate the level of RNA synthesis from the core promoter. The nuclear hormone receptors HNF4 and RXRalpha plus PPARalpha appear to have a critical role in governing pregenomic RNA synthesis from the core promoter in cell culture and probably represent a major determinant governing the hepatotropism of this virus. The level of 3.5-kb HBV RNA synthesis is approximately proportional to the level of viral replication in cell culture; however, this is not the case in the liver of HBV transgenic mice. Directly modulating the levels or activities of specific transcription factors known to regulate HBV transcription in cell culture can increase viral replication in HBV transgenic mice without greatly changing the levels of HBV transcripts. Various immune stimuli that alter transcription factor activities involved in regulating viral RNA synthesis can negatively affect viral replication without affecting HBV transcription. These observations suggest that in vivo very subtle changes in HBV transcription may contribute to large alterations, either negative or positive, in viral replication. Investigation of transcription factor-null HBV transgenic mice under various physiological conditions will be required to establish the putative role of specific transcription factors in regulating viral replication in vivo.
乙型肝炎病毒（HBV）通过3.5kb病毒前基因组RNA的逆转录进行复制。因此，前基因组RNA转录的调控是病毒生命周期中的关键步骤。各种普遍存在的和肝脏富集的转录因子已被证明可调节核心启动子的RNA合成水平。核激素受体HNF4和RXRα加PPARα似乎在细胞培养中调控核心启动子的前基因组RNA合成方面起着关键作用，并且可能是决定该病毒嗜肝性的主要因素。在细胞培养中，3.5kb HBV RNA的合成水平与病毒复制水平大致成正比；然而，在HBV转基因小鼠的肝脏中情况并非如此。直接调节已知在细胞培养中调控HBV转录的特定转录因子的水平或活性，可以增加HBV转基因小鼠中的病毒复制，而不会大幅改变HBV转录本的水平。各种改变参与调节病毒RNA合成的转录因子活性的免疫刺激，可以在不影响HBV转录的情况下对病毒复制产生负面影响。这些观察结果表明，在体内，HBV转录中非常细微的变化可能会导致病毒复制出现大幅改变，无论是负面的还是正面的。需要在各种生理条件下对转录因子缺失的HBV转基因小鼠进行研究，以确定特定转录因子在体内调节病毒复制中的假定作用。
