HBX PROTEIN AND HEPATITIS B VIRUS INFECTION

这项奖学金的目的是了解 土拨鼠乙肝病毒(WHV)HBx基因在病毒感染中的作用。这个 肝细胞癌与慢性乙肝感染的关系尚不清楚，但 病毒HBx蛋白被认为是一个重要因素。HBX既是 一种RAS和c-Src的胞质激活剂，以及一种核激活剂 某些转录元件，如WHV增强子。几个HBX 施耐德实验室之前已经描述过突变体，它将 对这项研究来说是无价的，因为它们将细胞质分离 HBX的活动来自于核活动。联谊会建议 了解HBx在WHV感染中的重要作用及其意义 参与了病毒的持续存在。这些研究不会调查 在转化的组织培养细胞中分离出HBx蛋白，但 取而代之的是啮齿动物肝脏外植体感染乙肝病毒期间。仅限于 研究HBx在该系统中WHV感染中的作用可以 由于WHV和乙肝病毒，HBx在感染中的真正作用有待研究 通常只感染含有肝脏特异性的原代肝细胞 可能在感染中发挥特殊作用的因素。研究 在连续的肝细胞组织培养细胞中进行，虽然有用， 因可能缺乏生物学相关性而受到批评。 因此，缺乏HBx基因的野生型WHV或突变型WHV基因组 将被转导到移植的原代肝细胞中 复制缺陷型腺病毒载体，并补充了 携带野生型或突变型HBx基因的反式HBx丢失(在Ad 向量)。

The objective of this fellowship is to understand the role of the woodchuck hepatitis B virus (WHV) HBx gene in viral infection. The association of HCC and chronic HBV infection is not well understood, but the viral HBx protein is thought to be an important factor. HBx is both a cytoplasmic activator of Ras and c-Src, and a nuclear activator of certain transcription elements such as the WHV enhancers. Several HBx mutants have been described previously from the Schneider lab that will be invaluable for this study, because they separate cytoplasmic activities of HBx from the nuclear activities. The fellowship proposes to understand the essential role of HBx in WHV infection and its involvement in viral persistence. These studies will not investigate HBx protein in isolation in transformed tissue culture cells, but instead during HBV infection of rodent liver explants. Only by investigating the role of HBx in WHV infection in this system can the real function of HBx in infection be studied, since WHV and HBV ordinarily only infect primary liver cells that contain liver specific factors which may play specialized roles in infection. Studies performed in continuous hepatocyte tissue culture cells, while useful,, have been criticised for possibly lacking biological relevance. Consequently, wildtype WHV or mutant WHV genomes which lack the HBx gene will be transduced into explanted primary hepatocytes by piggybacking on replication-defective adenovirus vectors, and complemented for the loss of HBx in trans with wildtype or mutant HBx genes (carried on Ad vectors).