IMMUNOPATHOGENESIS OF RUBELLA VIRUS ASSOCIATED AUTOIMMUNE DYSFUNCTION

自然感染风疹或免疫接种的并发症 成年女性风疹减毒疫苗包括暂时性和慢性 关节炎症状。因为25%的成人轮状病毒疫苗接种会导致急性 或成年女性的慢性关节炎，了解它是有用的 导致这些复杂情况的事件。这可能会导致 到RV疫苗接种的改进。为了理解分子 RV相关疾病的潜在机制，我们一直在研究 轮状病毒复制的机制。我们已经确定了顺式作用元件， 茎环结构存在于RV RNA的5‘和3’末端， 病毒复制所必需的。此外，我们还描述了 与这些元件相互作用的宿主编码的蛋白质。5‘(+)SL RV RNA结合蛋白是Ro/SS-A抗原的同源物，而 3‘(+)SL RV RNA结合蛋白是人钙网织蛋白的同源物。 此外，Ro-SSA自身抗原与5‘端结合的特性 经免疫沉淀法鉴定为La自身抗原 用单一特异性La人血清和兔抗血清 重组La.La与RV 5‘(+)SL RNA的特异性相互作用 在体外和体内都得到了证实。5‘(+)SL的重要性 利用荧光素在体内也证实了轮状病毒RNA的翻译 记者RNA报道。La抗原和钙网织蛋白与钙结合蛋白的相互作用 Rv rna具有临床意义，因为针对这些蛋白的抗体 在许多自身免疫性疾病中都有发现。我们已经调查了 各种自身免疫性疾病患者的人血清 功能障碍可以识别与细胞蛋白质相关的 RV RNAs。干燥综合征(SS)患者的一组血清 或系统性红斑狼疮(SLE)免疫沉淀RV RNA-蛋白质复合体。RV 5‘和3’(+)血清的反应性 SL RNA-蛋白质复合体与血清结合能力相关 识别La或Ro和La自身抗原。我们还观察到 轮状病毒感染者2年内显著的抗La活性 感染后。细胞抗原与轮状病毒的相关性 自身免疫中的顺式作用元件和抗体对顺式作用元件的反应 患者，提示类似的事件可能会发生在 自然感染或慢性轮状病毒感染后的自身免疫 免疫接种。目前，La抗原和钙网织蛋白的作用 了解慢性风疹病毒疫苗相关的病原学 关节病正在研究中。发布：Pogue，G.P.，Hofmann，J. 首页--期刊主要分类--期刊细介绍--期刊题录与文摘--期刊详细文摘内容 H.L.(1996)J.Virol.70,6269-6277。

Complications of natural rubella infection or immunization with attenuated rubella vaccine in adult women include transient and chronic arthritic symptoms. Because 25% of adult RV vaccinations result in acute or chronic arthritis in adult females, it would be useful to understand the events leading to these complications. Potentially this would lead to improvements in RV vaccination. In order to understand the molecular mechanisms underlying RV-associated disease, we have been studying the mechanism of RV replication. We have identified the cis-acting elements, stem-loop structures present at the 5' and 3' terminus of RV RNA, necessary for virus replication. Further, we have characterized the host-encoded proteins which interact with these elements. The 5' (+) SL RV RNA binding protein is a homologue of the Ro/SS-A antigen, whereas the 3' (+) SL RV RNA binding protein is a homologue of human calreticulin. Further, characterization of the Ro-SSA autoantigen binding to the 5' end of RV RNA, identified it as the La autoantigen by immunoprecipitation using mono-specific La human sera and a rabbit serum raised against recombinant La. Specific interaction of La with the RV 5' (+) SL RNA was demonstrated both in vitro and in vivo. The importance of the 5' (+) SL RV RNA in translation was also demonstrated in vivo using Lucifersae reporter RNA. The interaction of both La antigen and calreticulin with RV RNA is of clinical interest because antibodies to these proteins have been found in many autoimmune diseases. We have investigated whether human serum from individuals suffering from various autoimmune dysfunctions could recognize the cellular proteins associated with the RV RNAs. A subset of sera from individuals with Sjogren's syndrome (SS) or Systemic Lupus Erythematosus (SLE) immunoprecipitated the RV RNA-protein complexes. The reactivity of the sera with RV 5' and 3' (+) SL RNA-protein complexes correlated with the ability of the sera to recognize either the La or the Ro and La autoantigens. We also observed a significant anti-La activity in RV infected individuals 2 years post-infection. The association of cellular antigens with the RV cis-acting elements and antibody response to such complexes in autoimmune patients, suggest that similar events may occur at the initiation of autoimmunity in chronic RV infections following natural infections or immunization. Currently, the role of both the La antigen and calreticulin in understanding the etiology of chronic rubella virus vaccine-associated arthropathy is being investigated.Publication:Pogue, G. P., Hofmann, J., Duncan, R. D., Best, J. M., Etherington, J., Sontheimer, R. D., Nakhasi, H. L. (1996) J. Virol. 70, 6269-6277.