Lee T H, Finegold M J, Shen R F, DeMayo J L, Woo S L, Butel J S
Division of Molecular Virology, Baylor College of Medicine, Houston, Texas 77030.
J Virol. 1990 Dec;64(12):5939-47. doi: 10.1128/JVI.64.12.5939-5947.1990.
The hepatitis B virus X protein acts as a transcriptional transactivator in vitro. To elucidate possible biological effects of X protein on liver cells in vivo, we generated four lines of transgenic mice carrying the X gene open reading frame under the control of the human alpha-1-antitrypsin regulatory region. The plasmid construct used to introduce the transgene was shown to encode a 16-kDa X protein with transactivating capability. The expression of X protein was detectable in liver tissue of transgenic animals of three of the lines by immunoblot analysis; levels of expression were highest in the first month after birth of the animals. Over 80 animals from the expressing lines were examined histologically. Most transgenic mice, some of which were observed for up to 2 years, remained normal. However, a few transgenic animals developed mild focal hepatitis, nuclear pleomorphism, focal necrosis, and/or nodular hyperplasia in the liver. Increased mitotic activity of hepatocytes also was observed. We conclude that, at the level of expression achieved in these transgenic mice, the hepatitis B virus transcriptional transactivator X protein alone does not appear to mediate the development of serious liver damage or hepatocellular carcinomas.
乙肝病毒X蛋白在体外可作为转录反式激活因子。为阐明X蛋白在体内对肝细胞可能产生的生物学效应，我们构建了四系转基因小鼠，这些小鼠携带在人α-1-抗胰蛋白酶调控区控制下的X基因开放阅读框。用于导入转基因的质粒构建体显示可编码具有反式激活能力的16 kDa X蛋白。通过免疫印迹分析在三系转基因动物的肝脏组织中可检测到X蛋白的表达；在动物出生后的第一个月表达水平最高。对来自表达系的80多只动物进行了组织学检查。大多数转基因小鼠，其中一些观察了长达2年，仍保持正常。然而，少数转基因动物出现了轻度局灶性肝炎、核多形性、局灶性坏死和/或肝脏结节性增生。还观察到肝细胞有丝分裂活性增加。我们得出结论，在这些转基因小鼠所达到的表达水平上，单独的乙肝病毒转录反式激活因子X蛋白似乎并未介导严重肝损伤或肝细胞癌的发生。
