Tang Hong, McLachlan Alan
Department of Cell Biology, The Scripps Research Institute, La Jolla, California 92037, USA.
J Virol. 2002 Aug;76(15):7468-72. doi: 10.1128/jvi.76.15.7468-7472.2002.
Hepadnavirus replication occurs in hepatocytes in vivo and in hepatoma cell lines in cell culture. Hepatitis B virus (HBV) replication can occur in nonhepatoma cells when pregenomic RNA synthesis from viral DNA is activated by the expression of the nuclear hormone receptors hepatocyte nuclear factor 4 (HNF4) and the retinoid X receptor alpha (RXR alpha) plus peroxisome proliferator-activated receptor alpha (PPAR alpha) heterodimer. Nuclear hormone receptor-dependent HBV replication is inhibited by hepatocyte nuclear factor 3 (HNF3). In contrast, HNF3 and HNF4 support duck hepatitis B virus (DHBV) replication in nonhepatoma cells, whereas the RXR alpha-PPAR alpha heterodimer inhibits HNF4-dependent DHBV replication. HNF3 and HNF4 synergistically activate DHBV pregenomic RNA synthesis and viral replication. The conditions that support HBV or DHBV replication in nonhepatoma cells are not able to support woodchuck hepatitis virus replication. These observations indicate that avian and mammalian hepadnaviruses have distinct transcription factor requirements for viral replication.
嗜肝DNA病毒在体内的肝细胞以及细胞培养中的肝癌细胞系中进行复制。当病毒DNA的前基因组RNA合成被核激素受体肝细胞核因子4(HNF4)、视黄酸X受体α(RXRα)以及过氧化物酶体增殖物激活受体α(PPARα)异二聚体的表达激活时,乙型肝炎病毒(HBV)可在非肝癌细胞中复制。肝细胞核因子3(HNF3)可抑制核激素受体依赖性的HBV复制。相反,HNF3和HNF4可支持鸭乙型肝炎病毒(DHBV)在非肝癌细胞中的复制,而RXRα-PPARα异二聚体则抑制HNF4依赖性的DHBV复制。HNF3和HNF4协同激活DHBV前基因组RNA合成及病毒复制。支持HBV或DHBV在非肝癌细胞中复制的条件无法支持土拨鼠肝炎病毒的复制。这些观察结果表明,禽类和哺乳动物嗜肝DNA病毒对病毒复制具有不同的转录因子需求。