Araki K, Nishimura S, Ochiya T, Okubo K, Miyazaki J, Matsubara K, Yamamura K
Institute for Medical Genetics, Kumamoto University Medical School.
Jpn J Cancer Res. 1991 Mar;82(3):235-9. doi: 10.1111/j.1349-7006.1991.tb01834.x.
We have demonstrated by immunoelectron microscopy that 42-nm particles with double-shelled structures characteristic of Dane particles are present in the serum of transgenic mice, 1.2HB-BS 10, carrying partly duplicated hepatitis B virus (HBV) genome. Furthermore, these particles were shown to infect primary human fetal hepatocytes as demonstrated by the elevation of HBV surface antigen (HBsAg) in the culture medium. HBV DNA is known to be expressed in a liver- and kidney-specific manner in the adult mouse, so we examined the developmental expression of viral antigens. In the liver, viral antigens (HBsAg and HBV e antigen) began to be expressed before birth and the level of expression showed a sharp rise after birth. On the other hand, in the kidney, viral antigens began to be expressed after birth. Serum levels of viral antigens were roughly proportional to the levels of expression in the liver, suggesting that the liver is the main source for viral antigens in the serum. None of these transgenic mice produced anti-HBs or anti-HBV core response or showed biochemical or pathological change up to at least 24 months of age. All these results suggest that infectious viral particles can be produced in transgenic mice, and that expression and replication of HBV DNA are not toxic in vivo.
我们通过免疫电子显微镜证明，在携带部分重复乙肝病毒（HBV）基因组的转基因小鼠1.2HB - BS 10的血清中，存在具有 Dane 颗粒特征性双壳结构的42纳米颗粒。此外，如培养基中乙肝病毒表面抗原（HBsAg）升高所示，这些颗粒能够感染原代人胎儿肝细胞。已知HBV DNA在成年小鼠中以肝脏和肾脏特异性方式表达，因此我们研究了病毒抗原的发育表达情况。在肝脏中，病毒抗原（HBsAg和乙肝e抗原）在出生前就开始表达，出生后表达水平急剧上升。另一方面，在肾脏中，病毒抗原在出生后开始表达。病毒抗原的血清水平与肝脏中的表达水平大致成正比，这表明肝脏是血清中病毒抗原的主要来源。这些转基因小鼠在至少24个月龄之前均未产生抗 - HBs或抗 - HBV核心反应，也未出现生化或病理变化。所有这些结果表明，转基因小鼠能够产生感染性病毒颗粒，并且HBV DNA的表达和复制在体内没有毒性。
