PATHOGENESIS OF GROUND GLASS CELLS IN HEPATITIS B

乙肝病毒明显与肝细胞癌有关 癌症，但致癌的机制却知之甚少。 一种可能性是，最近的转基因小鼠研究加强了这一可能性 细胞坏死和再生在很大程度上有助于 致癌。在慢性乙肝感染中，出现了 所谓的毛玻璃细胞，也就是含有浓缩的乙肝病毒的细胞 内质网中的表面蛋白。磨砂玻璃电池 转基因小鼠可以造成足够的细胞损伤和肝脏 再生以诱发肝细胞癌。因此，我们会 我想研究人类的毛玻璃细胞是如何产生的 感染。我们的假设是，乙肝病毒的基因组重排 在慢性感染过程中几乎总是存在的DNA会导致 DYS调控病毒表面基因的转录。这又反过来， 导致大量表面蛋白的过度合成，这是 已知能够导致毛玻璃电池。我们将测试我们的 通过产生突变的乙肝病毒克隆并寻找表面基因来假说 DYS-瞬时基因的调控。我们将进一步确认 这些突变会导致培养细胞中的毛玻璃细胞和 转基因小鼠。希望这些研究将导致新的 对毛玻璃细胞发病机制的见解，并最终 乙肝病毒感染中的肝细胞癌。

Hepatitis B virus (HBV) is clearly associated with hepatocellular carcinomas, yet the mechanism of carcinogenesis is poorly understood. One possibility, strengthened by recent transgenic mouse studies, is that cellular necrosis and regeneration contribute significantly to carcinogenesis. In chronic HBV infection, there is appearance of so-called ground glass cells, which are cells with inspissated HBV surface proteins in the endoplasmic reticulum. Ground glass cells in transgenic mice can cause sufficient cellular damage and hepatic regeneration to induce hepatocellular carcinomas. Therefore, we would like to investigate how ground glass cells are produced in human infections. Our hypothesis is that genomic rearrangements of the HBV DNA, almost invariably present during chronic infection, cause dys-regulated transcription of the viral surface gene. This, in turn, leads to over synthesis of the large form of the surface protein, which is known to be capable of causing ground glass cells. We will test our hypothesis by generating mutant HBV clones, and looking for surface gene dys-regulation by transient transfections. We will further confirm that these mutations can cause ground glass cells in cultured cells and transgenic mice. It is hoped that these studies will lead to new insights on the pathogenesis of ground glass cells, and ultimately of hepatocellular carcinoma in HBV infection.