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（由申请人提供）：甲状腺病毒，例如Chickungunya和Ross River病毒（RRV），是全球疾病的重要原因。尽管对α病毒引起的关节炎的发病机理知之甚少，但与先天免疫系统的病毒相互作用可能会导致疾病。因此，我们建议在RRV诱导的炎症的小鼠模型中表征先天炎症介质（例如细胞因子，趋化因子和模式识别受体）的作用。我们提出以下特定目标。 1）表征炎症细胞因子和趋化因子对体内和体外RRV感染的反应。 2）确定IFN-GAMMA在RRV诱导的疾病中的作用。与野生型小鼠不同的IFN-y缺陷小鼠将不会出现严重的疾病，将用于研究IFN-Gamma在RRV发病机理中的作用。将研究RRV感染小鼠中IFN-GAMMA的细胞来源。 3）研究模式识别受体在RRV诱导的炎症和免疫反应中的作用。 Toll样受体和含卡的RNA Helicase Rig-1将被评估，以使用转染系统和RNAi技术在体外识别Ross River病毒感染中的作用。其他研究将阐明引起炎症反应的病毒成分。