PATHOGENESIS OF RETROVIRUS INDUCED ARTHRITIS

山羊接种逆转录病毒--山羊关节炎-脑炎病毒 (CAEV)，会导致进行性炎症性关节炎，符合大多数 类风湿关节炎的诊断标准。这个项目的最初目标是 建议是确定病毒如何在人体内引起炎症反应 关节和免疫反应是否有因果关系。传染性病毒， 病毒蛋白质和病毒遗传信息将在 接种山羊，并与关节炎的严重程度进行比较。免疫抑制 山羊将被用来建立免疫反应和 病变的发展。如果存在关系，则 将研究免疫发病机制。慢性关节炎的进展将是 关于病毒持久性和自身免疫机制的研究 回应。关于病毒的持久性，我们将检验这一假设 整合的前病毒存在于免疫系统检测不到的细胞中， 抗原变异体的周期性发展刺激免疫反应和 使疾病永久化由自身免疫现象引起的病变进展将是 寻找类风湿因子和其他多克隆证据 激活免疫细胞。本提案目标的实现应 为理解持续病毒引起的关节炎提供依据 感染，以及达到治疗或预防类似疾病的目标的先决条件 人的疾病。

Inoculation of goats with a retrovirus, caprine arthritis-encephalitis virus (CAEV), causes a progressive inflammatory arthritis that fulfills most of the diagnostic criteria for rheumatoid arthritis. The initial objectives of this proposal are to determine how the virus causes the inflammatory response in the joint and whether the immune response is causally involved. Infectious virus, viral proteins and viral genetic information will be measured in the joints of inoculated goats and compared with the severity of arthritis. Immunosuppressed goats will be used to establish the relationship between the immune response and the development of lesions. If a relationship exists, mechanisms of the immunopathogenesis will be studied. Progression of chronic arthritis will be studied with respect to mechanisms involving virus persistence and autoimmune responses. With regard to virus persistence, we will test the hypothesis that integrated provirus exists in cells undetected by the immune system and that periodic development of antigenic variants stimulate immune responses and perpetuate disease. Lesion progression by autoimmune phenomena will be approached by a search for rheumatoid factor and other evidence of polyclonal activation of immunocytes. Accomplishment of the aims of this proposal should provide a basis for comprehension of arthritis caused by persistent viral infection, and prerequisite to the goal of treatment or prevention of similar disease of people.