CAPRINE ARTHRITIS ENCEPHALITIS VIRUS INFECT: IMMUNITY, GENOME: GOAT AIDS MODEL

山羊关节炎脑炎病毒(CAEV)属于 慢病毒属逆转录病毒的亚家族。它集成到主机中 细胞基因组，并诱导家山羊持续感染。 CAEV感染可引起幼山羊脑脊髓炎和乳房炎， 成年山羊慢性进行性关节炎和滑膜炎。这个 病理上与类风湿性关节炎相似的关节炎 人类的关节炎(RA)。最近有证据表明，一种新型的CAEV 变异体发生在人类身上，并产生免疫交叉反应 人类免疫缺陷病毒I型(IUV-1)。很明显，CAEV是 重要的不仅是作为山羊的病原体，而且作为传播 研究人类疾病。我们将在山羊身上使用CAEV诱导的疾病 作为研究慢病毒致病机制的模型 也是为了进一步调查一些导致 关节炎。这项拟议项目的目的是研究 CAEV致病的分子机制。这一点在 CAEV-1样慢病毒作为预防用药的可能性 抗人类病毒的药物，如EDIV-1。具体来说，我们建议： 一)调查病毒与宿主细胞的相互作用，确定和 细胞表面受体的鉴定(S)和确定病毒的作用 GP 13 5和I Do THA是与细胞相互作用所必需的 受体；以及ii)研究可能涉及的一些机制 通过确定血管紧张素转换酶的作用研究关节炎的发生和发展 各种细胞因子和趋化因子，氧自由基，细胞内 钙波动、循环免疫复合体、类风湿因子 还通过鉴定差异转录的基因 在感染期间。这些结果将提供更好的 了解与类风湿性关节炎非常相似的疾病状况 其病因是已知的。

Caprine arthritis encephalitis virus (CAEV) belongs to the lentivirus subfamily of retroviruses. It integrates into the host cell genome and induces a persistent infection of domestic goats. CAEV infection causes encephalomyelitis in young goats, and mastitis, chronic progressive arthritis and synovitis in adult goats. The arthritis which results is similar in pathology to rheumatoid arthritis (RA) in humans. There is recent evidence that a novel CAEV variant occurs in humans and generates immune cross-reactivity to human immunodeficiency virus- I (IUV- 1). It is evident that CAEV is important not only as a pathogen in goats but as a vehicle for studying human diseases. We will use CAEV-induced disease 'in goats as a model to study the pathogenetic mechanisms of lentiviruses and also to investigate further some of the mechanisms that lead to arthritis. The obiective of this proposed project is to study molecular mechanisms of CAEV pathogenesis. This is important in the light of the possible use of CAEV-1ike lentivuiuses as -prophylactic agents against human viruses like EDIV-1. Specifically we propose to: i) investigate virus-host cell interactions by identifying and characterizing cell surface receptor(s) and defining the role of viral gp 13 5 and i do tha are essential for interaction with the cellular receptors; and ii) investigate some mechanisms that may be involved in the initiation and progression of arthritis by determining the role of various cytokines and chemokines, oxygen radicals, intracellular calcium fluctuations, circulating immune complexes, rheumatoid factor and also by identifying genes that are differentially transcribed during the infection. These results will provide a better understanding of a disease condition that is very similar to RA and in which the etiology is known.