PATHOGENESIS OF RETROVIRUS INDUCED ARTHRITIS

用逆转录病毒山羊关节炎-脑炎病毒接种山羊 （CAEV），导致进行性炎症性关节炎，满足大多数的 类风湿关节炎的诊断标准。 这一初步目标 这项研究的目的是确定病毒是如何引起炎症反应的。 关节和免疫反应是否有因果关系。 传染性病毒， 病毒蛋白和病毒遗传信息将在关节中测量， 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之间的关系， 病变的发展。 如果存在关系， 将研究免疫发病机理。 慢性关节炎的进展将是 研究涉及病毒持续存在和自身免疫的机制 应答 关于病毒的持久性，我们将检验以下假设： 整合的前病毒存在于免疫系统检测不到的细胞中， 抗原变体的周期性发展刺激免疫应答， 使疾病永久化。 由自身免疫现象引起的病变进展将是 通过寻找类风湿因子和其他多克隆证据， 免疫细胞的激活。 实现本建议的目标应 为认识持续性病毒性关节炎提供依据 感染，以及治疗或预防类似感染目标的先决条件 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.