PATHOGENESIS OF GROUND GLASS CELLS IN HEPATITIS B

B型肝炎病毒（HBV）与肝细胞癌明显相关， 癌症，但致癌机制知之甚少。 最近的转基因小鼠研究加强了一种可能性， 细胞坏死和再生对 致癌作用 在慢性HBV感染中， 所谓的毛玻璃细胞，即HBV感染的细胞 内质网中的表面蛋白。 毛玻璃细胞 转基因小鼠可以引起足够的细胞损伤和肝脏损伤， 再生以诱导肝细胞癌。 因此，我们将 我喜欢研究毛玻璃细胞是如何在人体内产生的， 感染. 我们的假设是HBV的基因组重排 DNA，几乎总是存在于慢性感染，导致 病毒表面基因的转录失调。 这反过来又 导致表面蛋白质的大形式的过度合成， 会导致毛玻璃细胞 我们将测试我们的 通过产生突变的HBV克隆，并寻找表面基因， 瞬时转染引起的调节异常。 我们将进一步确认， 这些突变可导致培养细胞中的毛玻璃细胞， 转基因小鼠 希望这些研究将导致新的 毛玻璃细胞发病机制的见解，并最终 HBV感染与肝癌

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.