Nipah Virus Pathobiology and Effects on Innate Immunity
尼帕病毒病理学及其对先天免疫的影响
基本信息
- 批准号:6915278
- 负责人:
- 金额:$ 38.54万
- 依托单位:
- 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:2005-03-15 至 2010-02-28
- 项目状态:已结题
- 来源:
- 关键词:Nipah virusantigen presentationbioterrorism /chemical warfarecarbohydrate structurecell fusioncell linechemical structure functionclinical researchdendritic cellsemerging infectious diseaseflow cytometrygene expressiongenetic manipulationhost organism interactionhuman tissueimmune responseimmunitylectinoligosaccharidesprotein protein interactionprotein structurevirulencevirus geneticsvirus infection mechanismvirus protein
项目摘要
The Nipah virus (NiV) is an emerging viral pathogen, classified as a Category C pathogen of the NIAID Biodefense Research Agenda. NiV infects agricultural livestock and humans; in 1999, NiV infection among agricultural workers in Malaysia and Singapore resulted in a 40% mortality rate and loss of livestock worth over $100 million. NiV is a member of a new genus of paramyxoviruses, and little is known about NiV biology or the immune response to NiV.
However, autopsy studies of NiV victims found that the virus targets lymph nodes and endothelial cells with endothelial syncytia formation being the pathologic hallmark of NiV infection. Cell fusion and syncytia formation depend on expression of the NiV F and G envelope glycoproteins. We have found that syncytia formation is regulated by glycosylation of these envelope glycoproteins, with specific N-glycans on NiV F and G playing important roles in cell
fusion. Importantly, we have also found that cell fusion can be blocked by galectin-1, an endogenous lectin of the innate immune system that is expressed by endothelial cells and dendritic cells. In addition, we have made the novel observation that galectin-1 induces robust pro-inflammatory cytokine secretion by monocyte derived dendritic cells, an effect that may augment an antiviral immune response. Our driving hypothesis for this proposal is that glycan structures on the NiV F and G glycoproteins. and the innate immune lectin galectin-1 that recognizes these structures, are critical determinants in the pathogenesis of this viral disease. Our Specific Aims are: (1) Determine structural features of oligosaccharides on the F and G env glycoproteins that are critical for glycoprotein expression and syncytia formation, (2) Elucidate the mechanism by which galectin-1 regulates NiV envelope glycoprotein-mediated cell fusion, (3)
Characterize the structural features involved in binding to and fusion of target cells, (4) Examine the effects of galectin-1 on soluble mediators of the innate and adaptive immune response.
This work will address critical issues for rapid development of strategies to enhance innate immune responses to this emerging viral pathogen. The co-investigators have a unique combination of expertise, and propose an innovative set of studies into the glycobiology of NiV pathogenesis.
尼帕病毒(NiV)是一种新兴的病毒病原体,被列为NIAID生物防御研究议程的C类病原体。NiV感染农业牲畜和人类; 1999年,马来西亚和新加坡农业工人中的NiV感染导致40%的死亡率和价值超过1亿美元的牲畜损失。NiV是副粘病毒属的一个新成员,关于NiV生物学或对NiV的免疫应答知之甚少。
然而,NiV受害者的尸检研究发现,病毒靶向淋巴结和内皮细胞,内皮合胞体形成是NiV感染的病理标志。细胞融合和合胞体的形成依赖于NiV F和G包膜糖蛋白的表达。我们发现合胞体的形成受这些包膜糖蛋白糖基化的调节,NiV F和G上的特异性N-聚糖在细胞中起重要作用。
核聚变重要的是,我们还发现细胞融合可以被半乳糖凝集素-1阻断,半乳糖凝集素-1是由内皮细胞和树突状细胞表达的先天免疫系统的内源性凝集素。此外,我们还发现半乳糖凝集素-1通过单核细胞衍生的树突状细胞诱导强的促炎细胞因子分泌,这是一种可能增强抗病毒免疫应答的作用。我们对这一提议的驱动假设是NiV F和G糖蛋白上的聚糖结构。和识别这些结构的先天免疫凝集素半乳糖凝集素-1是这种病毒性疾病发病机制的关键决定因素。我们的具体目标是:(1)确定F和G env糖蛋白上寡糖的结构特征,其对于糖蛋白表达和合胞体形成至关重要,(2)阐明半乳糖凝集素-1调节NiV包膜糖蛋白介导的细胞融合的机制,(3)
鉴定与靶细胞结合和融合有关的结构特征。(4)检测半乳糖凝集素-1对先天性和适应性免疫应答的可溶性介质的影响。
这项工作将解决快速发展战略的关键问题,以增强对这种新出现的病毒病原体的先天免疫反应。共同研究者拥有独特的专业知识组合,并提出了一套创新的研究NiV发病机制的糖生物学。
项目成果
期刊论文数量(0)
专著数量(0)
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Linda G Baum其他文献
Linda G Baum的其他文献
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{{ truncateString('Linda G Baum', 18)}}的其他基金
Regulation of inflammatory cell migration in asthma
哮喘炎症细胞迁移的调节
- 批准号:
8063630 - 财政年份:2010
- 资助金额:
$ 38.54万 - 项目类别:
Regulation of inflammatory cell migration in asthma
哮喘炎症细胞迁移的调节
- 批准号:
7911394 - 财政年份:2010
- 资助金额:
$ 38.54万 - 项目类别:
Overcoming tumor cell resistance to apoptosis with a natural product, GCS-100
用天然产物 GCS-100 克服肿瘤细胞对细胞凋亡的抵抗
- 批准号:
7821317 - 财政年份:2009
- 资助金额:
$ 38.54万 - 项目类别:
Overcoming tumor cell resistance to apoptosis with a natural product, GCS-100
用天然产物 GCS-100 克服肿瘤细胞对细胞凋亡的抵抗
- 批准号:
7640481 - 财政年份:2009
- 资助金额:
$ 38.54万 - 项目类别:
Nipah Virus Pathobiology and Effects on Innate Immunity
尼帕病毒病理学及其对先天免疫的影响
- 批准号:
7027741 - 财政年份:2005
- 资助金额:
$ 38.54万 - 项目类别:
Nipah Virus Pathobiology and Effects on Innate Immunity
尼帕病毒病理学及其对先天免疫的影响
- 批准号:
7406028 - 财政年份:2005
- 资助金额:
$ 38.54万 - 项目类别:
Nipah Virus Pathobiology and Effects on Innate Immunity
尼帕病毒病理学及其对先天免疫的影响
- 批准号:
7214116 - 财政年份:2005
- 资助金额:
$ 38.54万 - 项目类别:
Nipah Virus Pathobiology and Effects on Innate Immunity
尼帕病毒病理学及其对先天免疫的影响
- 批准号:
7569493 - 财政年份:2005
- 资助金额:
$ 38.54万 - 项目类别:
A Novel Cell Death Pathway Induced by Galectin-1
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6753612 - 财政年份:1997
- 资助金额:
$ 38.54万 - 项目类别:
A Novel Cell Death Pathway Induced by Galectin-1
Galectin-1 诱导的新型细胞死亡途径
- 批准号:
6370407 - 财政年份:1997
- 资助金额:
$ 38.54万 - 项目类别:
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