HBX PROTEIN AND HEPATITIS B VIRUS INFECTION

HBX 蛋白与乙型肝炎病毒感染

• 批准号: 6173020
• 负责人: Michael J Bouchard
• 金额: $ 3.92万
• 依托单位: NEW YORK UNIVERSITY SCHOOL OF MEDICINE
• 依托单位国家: 美国
• 财政年份: 2000
• 资助国家: 美国
• 起止时间: 2000-06-01 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/6173020
• 关键词: Adenoviridae; Rodentias; animal tissue; biological signal transduction; cell line; cell nucleus; cytoplasm; gene expression; genetic promoter element; hepatitis B; hepatitis B virus group; liver cells; marmots; mutant; tissue /cell culture; transcription factor; virus protein; virus replication

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).

该团契的目的是了解 病毒感染中的Woodchuck肝炎病毒（WHV）HBX基因。这 HCC和慢性HBV感染的关联尚不清楚，但 病毒HBX蛋白被认为是重要因素。 HBX都是 RAS和C-SRC的细胞质激活剂，以及 某些转录元素，例如WHV增强剂。 几个HBX 先前从施耐德实验室描述了突变体 对于这项研究是无价的，因为它们分离了细胞质 HBX的活动来自核活动。 奖学金提出 了解HBX在WHV感染中的重要作用及其 参与病毒持久性。 这些研究不会调查 在转化的组织培养细胞中分离的HBX蛋白，但 相反，在啮齿动物肝外植体的HBV感染期间。 仅由 调查HBX在WHV感染中的作用，可以 由于WHV和HBV，研究了HBX在感染中的实际功能 通常仅感染包含肝脏特异性的原发性肝细胞 可能在感染中扮演专门角色的因素。 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或突变体WHV基因组 将通过piggy养 在复制缺陷腺病毒载体上，并补充了 用野生型或突变体HBX基因trans中HBX的丧失（在AD上携带 向量）。