WOODCHUCK VIRUS--MOLECULAR BIOLOGICAL STUDIES

土拨鼠肝炎病毒(WHV)在分类学和血清学上是 与乙肝病毒(乙肝病毒)有关。感染其中的每一种 病毒与急慢性肝炎和肝细胞有关 它们各自宿主中的癌症和这些关联似乎是 本质上是病因性的。因此，土拨鼠感染WHV提供了一种 了解人类乙肝病毒感染的相关和方便的模型。 成功地完成了以下实验：(1)重组WHV 将DNA导入易感土拨鼠和急性黄鼠的肝脏。 产生慢性WHV感染。该病毒的完整核苷酸序列 检测感染性WHV DNA。(2)血清池制备自 长期感染的动物将用于未来的实验。病毒 在这些混合血清中出现的代表相当于“斑块净化” 病毒在我们的模型系统中。(3)WHV复制突变率为 估计每年每个基因组有2 x 10(-4)个变化，这是更低的 比其他病毒的突变率更高，这些病毒的聚合酶也缺乏 关联校对功能。(4)土拨鼠原代肝细胞 建立了用于转基因实验的组织培养系统。

The woodchuck hepatitis virus (WHV) is taxonomically and serologically related to the hepatitis B virus (HBV). Infection with each of these viruses is associated with acute and chronic hepatitis and hepatic cell carcinoma in their respective hosts and these associations appear to be etiological in nature. Thus, WHV infection of woodchucks provides a relevant and convenient model for understanding HBV infections of humans. The following experiments were successfully completed: (1) Recombinant WHV DNA was transfected into the liver of susceptible woodchucks and acute and chronic WHV infections were produced. The complete nucleotide sequence of the infectious WHV DNA was determined. (2) Serum pools were prepared from chronically infected animals to be used in future experiments. The virus present in these pooled sera represents the equivalent of "plaque purified" virus in our model system. (3) The mutation rate for WHV replication was estimated to be <2 x 10(-4) changes per genome per year, which is lower than the mutation rate of other viruses whose polymerase also lacks an associated proof-reading function. (4) A primary woodchuck hepatocyte tissue culture system was developed for use in transfection experiments.