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Pathogenesis of alphavirus-induced arthritis in mice.

甲病毒诱导的小鼠关节炎的发病机制。

基本信息

批准号：
7227107
负责人：
Thomas E Morrison
金额：
$ 4.99万
依托单位：
UNIV OF NORTH CAROLINA CHAPEL HILL
依托单位国家：
美国
项目类别：
财政年份：
2005
资助国家：
美国
起止时间：
2005-05-15 至 2008-05-14
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/7227107
关键词：
Ablation Alphavirus Arthralgia Arthritis Arthropods CCL2 gene Caspase Development Disease Disease Outcome Encephalitis Endosteum Fellowship Fever Fibroblasts Goals Human Immune Immune response Immune system In Vitro Individual Infection Infiltration Inflammation Inflammatory Inflammatory Infiltrate Inflammatory Response Integration Host Factors Interferon Type II Investigation Joints Laboratories Leg Limb structure Link Mediator of activation protein Mus Muscle Muscle Fibers Names Nature Numbers Osteoblasts Outcome Pathogenesis Pattern Recognition Pattern recognition receptor Periosteum Play Polyarthritides Production Proteins RNA Helicase RNA Interference RNA Viruses Reaction Research Design Rivers Role Ross river virus Severity of illness Signal Pathway Source Striated Muscles System Technology Tissues Toll-Like Receptor Pathway Toll-like receptors Transfection Up-Regulation Viral Viral Pathogenesis Virus Virus Diseases Virus Replication Wild Type Mouse cell type chemokine cytokine in vivo macrophage microbial mouse model pathogen positional cloning receptor research study response virus pathogenesis

项目摘要

DESCRIPTION (provided by applicant): Alphaviruses, such as Chickungunya and Ross River virus (RRV), are a significant cause of disease worldwide. Though the pathogenesis of alphavirus-induced arthritides is poorly understood, viral interactions with the innate immune system likely contribute to disease. Therefore, we propose to characterize the role of innate inflammatory mediators, such as cytokines, chemokines, and pattern recognition receptors, in a mouse model of RRV-induced inflammation. We propose the following specific aims. 1) Characterize the inflammatory cytokine and chemokine response to RRV infection in vivo and in vitro. 2) Determine the role of IFN-gamma in RRV-induced disease. IFN-y-deficient mice, which unlike wild-type mice do not develop severe disease, will be used to investigate IFN-gamma's role in RRV pathogenesis. Cellular sources of IFN-gamma in RRV-infected mice will be investigated. 3) Investigate the role of pattern recognition receptors in RRV-induced inflammatory and immune responses. Toll-like receptors and the CARD-containing RNA helicase RIG-1 will be evaluated for their role in recognizing Ross River virus infection in vitro using transfection systems and RNAi technology. Additional studies will elucidate viral components that elicit inflammatory responses.

描述(申请人提供)：甲型病毒，如基孔肯雅病毒和罗斯河病毒(RRV)，是全世界疾病的重要原因。虽然甲型病毒诱导的关节炎的发病机制尚不清楚，但病毒与先天免疫系统的相互作用可能导致疾病。因此，我们建议表征先天炎症介质的作用，如细胞因子、趋化因子和模式识别受体，在RRV诱导的炎症小鼠模型中。我们提出了以下具体目标。1)研究RRV在体内和体外对炎性细胞因子和趋化因子的反应。2)确定干扰素-γ在RRV诱导的疾病中的作用。与野生型小鼠不同，干扰素-γ缺陷小鼠不会发展成严重的疾病，将被用来研究干扰素-γ在轮状病毒发病中的作用。将调查RRV感染小鼠体内干扰素-γ的细胞来源。3)探讨模式识别受体在RRV诱导的炎症和免疫反应中的作用。Toll样受体和含有卡片的RNA解旋酶RIG-1将利用转染系统和RNAi技术在体外识别罗斯河病毒感染方面的作用进行评估。其他研究将阐明引起炎症反应的病毒成分。