Balsano C, Billet O, Bennoun M, Cavard C, Zider A, Grimber G, Natoli G, Briand P, Levrero M
Laboratoire de Genetique et Pathologie Experimentale, INSERM CJF 90-03, Institut Cochin de Genetique Moleculaire, Paris, France.
J Hepatol. 1994 Jul;21(1):103-9. doi: 10.1016/s0168-8278(94)80144-4.
It has previously been shown that the hepatitis B virus X gene product, pX, transactivates homologous and heterologous transcriptional regulatory sequences of viruses and various cellular genes in vitro. However, there is no evidence about the reproducibility and the relevance of this phenomenon in vivo. In this study we crossbred transgenic mice expressing the X gene under the control of the human antithrombin III (ATIII) gene regulatory sequences with transgenics carrying either the chloramphenicol acetyl-transferase or the LacZ bacterial reporter genes driven by the HIV1-LTR, which is known to be activated in trans by pX. Expression of pX in the liver stimulates the HIV1-LTR driven expression of both chloramphenicol acetyl-transferase and beta-galactosidase reporter genes in double transgenic mice. No detectable increase in chloramphenicol acetyl-transferase expression was observed in tissues, such as the spleen, brain and heart, that do not express pX. Our results confirm the transactivating properties of pX in vivo for the first time and support the hypothesis that pX might indeed modify gene expression in HBV-infected hepatocytes and influence viral pathogenesis.
先前已有研究表明，乙型肝炎病毒X基因产物pX在体外可反式激活病毒的同源和异源转录调控序列以及各种细胞基因。然而，尚无证据表明这种现象在体内具有可重复性及相关性。在本研究中，我们将在人抗凝血酶III（ATIII）基因调控序列控制下表达X基因的转基因小鼠与携带由HIV1-LTR驱动的氯霉素乙酰转移酶或LacZ细菌报告基因的转基因小鼠进行杂交，已知HIV1-LTR可被pX反式激活。在双转基因小鼠中，肝脏中pX的表达可刺激HIV1-LTR驱动的氯霉素乙酰转移酶和β-半乳糖苷酶报告基因的表达。在不表达pX的组织（如脾脏、大脑和心脏）中，未观察到氯霉素乙酰转移酶表达有可检测到的增加。我们的结果首次证实了pX在体内的反式激活特性，并支持了pX可能确实会改变HBV感染肝细胞中的基因表达并影响病毒发病机制这一假说。
