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

山羊关节炎脑炎病毒（CAEV）属于 逆转录病毒的慢病毒亚科。 它会融入宿主 细胞基因组并诱导家养山羊的持续感染。 CAEV感染引起幼山羊脑脊髓炎和乳腺炎， 成年山羊慢性进行性关节炎和滑膜炎。 的 关节炎的病理结果与类风湿性关节炎相似 类风湿关节炎（RA） 最近有证据表明，一种新的CAEV 变异发生在人类，并产生免疫交叉反应， 人类免疫缺陷病毒- I（IUV- 1）。 很明显，CAEV是 不仅是山羊的病原体， 研究人类疾病。 我们将在山羊中使用CAEV诱导的疾病 作为研究慢病毒致病机制的模型， 也进一步调查一些机制，导致 关节炎 本项目的目的是研究 CAEV致病的分子机制。 这一点在 鉴于CAEV-1样慢病毒可能用作预防性药物， 针对人类病毒如EDIV-1的药剂。 具体而言，我们建议： i）通过鉴定和鉴定来研究病毒-宿主细胞相互作用， 表征细胞表面受体并确定病毒的作用 gp 135和i do是与细胞相互作用所必需的。 受体;和ii）研究可能涉及的一些机制， 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，循环免疫复合物，类风湿因子 也可以通过识别那些在基因组中 在感染期间。 这些结果将提供更好的 了解与RA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.