Banks Krista E, Anderson Aimee L, Tang Hong, Hughes Douglas E, Costa Robert H, McLachlan Alan
Department of Cell Biology, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037, USA.
J Virol. 2002 Dec;76(24):12974-80. doi: 10.1128/jvi.76.24.12974-12980.2002.
Hepatitis B virus (HBV) transgenic mice expressing rat hepatocyte nuclear factor 3beta (HNF3beta) were generated by breeding HBV transgenic mice with transgenic mice that constitutively overexpress the rat HNF3beta polypeptide in the liver. HBV 3.5-, 2.4- and 2.1-kb transcripts were reduced 2- to 4-fold in these mice relative to the HBV transgenic mouse controls. In contrast, the abundance of viral replication intermediates was profoundly reduced in HBV transgenic mice by overexpression of HNF3beta. This results, in part, from the preferential reduction in the level of the pregenomic 3.5-kb RNA relative to the precore 3.5-kb RNA. Therefore, it is apparent that increased expression of HNF3beta modestly reduces viral transcription and dramatically inhibits replication in vivo in the HBV transgenic mouse. This suggests that altering the activity of this transcription factor in vivo in chronic HBV carriers might be therapeutically beneficial.
通过将乙肝病毒（HBV）转基因小鼠与在肝脏中组成型过表达大鼠肝细胞核因子3β（HNF3β）多肽的转基因小鼠杂交，培育出了表达大鼠HNF3β的HBV转基因小鼠。相对于HBV转基因小鼠对照，这些小鼠中的HBV 3.5 kb、2.4 kb和2.1 kb转录本减少了2至4倍。相比之下，通过过表达HNF3β，HBV转基因小鼠中病毒复制中间体的丰度显著降低。这部分是由于相对于前核心3.5 kb RNA，前基因组3.5 kb RNA水平优先降低所致。因此，很明显，HNF3β表达增加适度降低了病毒转录，并显著抑制了HBV转基因小鼠体内的复制。这表明，在慢性HBV携带者体内改变这种转录因子的活性可能具有治疗益处。
