VIRUSES OF HEPATITIS B AND GROUND SQUIRREL HEPATITIS

我们建议继续努力，以确定多肽和DNA的特征 乙型肝炎病毒及其与肝细胞关系的研究 癌症。我们最近发现了一种具有类似超微结构的病毒， 野生比奇黄鼠的抗原性、分子生物学特性 (地鼠肝炎病毒或GSHV)被困在加利福尼亚州北部。我们 建议建立一种类似于乙肝病毒的感染动物模型 并确定感染和相关疾病的自然病史。我们 将比较这两种病毒的抗原性和分子结构 尝试用病毒和病毒DNA感染培养中的细胞。我们 将尝试大量生产乙肝表面抗原(HBs Ag) 通过将主要乙肝表面抗原多肽基因导入细胞培养 细胞作为带有SV 40启动子的质粒载体的一部分。在此生产的乙肝表面抗原 Way将进行免疫原性测试，并被评估为潜在的乙肝疫苗。 这一方法将被用来尝试识别HBVDNA中的编码区 其他病毒基因产品。将尝试制造出克隆人 抗-HBs作为乙肝被动免疫的潜在来源。

We propose to continue our efforts to characterize the polypeptides and DNA of hepatitis B virus (HBV) and to study its relationship to hepatocellular carcinoma. We have recently discovered a virus with similar ultrastructural, antigenic, molecular and biological features in wild Beechey ground squirrels (ground squirrel hepatitis virus or GSHV) trapped in Northern California. We propose to develop this animal model of infection with a virus similar to HBV and determine the natural history of infections and the associated diseases. We will compare the antigenic and molecular structures of the two viruses and attempt to infect cells in culture with both viruses and the viral DNAs. We will attempt to produce hepatitis B surface antigen (HBsAg) in large quantities in cell culture by introducing the gene for the major HBsAg polypeptide into cells as part of a plasmid vector with SV 40 promotors. HBsAg produced in this way will be tested for immunogenicity and assessed as a potential HBV vaccine. This approach will be used to attempt to identify coding regions in HBV DNA for other viral gene products. Attempts will be made to produce monoclonal human anti-HBs as a potential source for passive immunization against HBV.