ANTIGENIC STRUCTURE OF HEPATITIS A VIRUS

甲型肝炎病毒的研究。 甲型肝炎病毒（HAV）是一种 piconavirus家族，但与其他病毒的亲缘关系较远， 将被归入自己的属。 虽然该病毒已 已经在几个实验室中克隆和测序，有用的肽或 多肽抗原尚未产生。 在早期的工作中，我们和 其他人已经表明，表达的HAV肽没有用， 表明HAV的天然抗原 可能是非线性的或构象依赖性的。 杰克斯台普顿博士 爱荷华州的大学已经插入了HAV的完整编码区， 我们的全长克隆到牛痘病毒表达载体中。似乎 这种构建体表达的HAV蛋白经过加工， 部分组装以形成天然抗原颗粒结构。 这 这种材料已经被制成疫苗，我们很快就会 在黑猩猩身上进行的初步试验 我们正在黑猩猩模型中研究T细胞对HAV的免疫力。 以下 感染HAV后，获得肝脏浸润淋巴细胞， 已经分离出特异性杀伤T细胞系。 表位正在被 通过使用牛痘表达克隆进行分析。 甲型肝炎特异性B细胞系 已经通过用EB转化黑猩猩PBL建立了 病毒 辅助性T细胞系是通过刺激T细胞 纯化的HAV。

Studies on hepatitis A virus. Hepatitis A virus (HAV) is a member of the piconavirus family but is distantly related to other viruses in that family and will be classified into its own genus. While the virus has been cloned and sequenced in several laboratories, useful peptide or polypeptide antigens have not been produced. In earlier work we and others have shown that expressed peptides of HAV are not useful as immunogens for the whole virus indicating that the native antigens of HAV are probably non-linear or conformation dependant. Dr. Jack Stapleton of the University of Iowa has inserted the complete coding region of HAV from our full length clone into a vaccinia virus expression vector. It appears that this construct expresses HAV proteins that are processed and at least partially assembled to form native antigenic particulate structures. This material has been formulated as a vaccine and we will soon be doing preliminary tests with it in chimpanzees. We are studying T-cell immunity to HAV in the chimpanzee model. Following infection by HAV, liver-infiltrating lymphocytes were obtained and specific killer T cell lines have been isolated. Epitopes are being analyzed by use of vaccinia expression clones. HAV specific B cell lines have been established by transformation of the chimpanzee PBL's with EB virus. Helper T-cell lines are being established by stimulating T-cells with purified HAV.