权益分类	功能权益	普通用户	{{item.name}}会员
{{category.name}}	{{benefitItem.name}}

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：
7569493
负责人：
Linda G Baum
金额：
$ 35.93万
依托单位：
UNIVERSITY OF CALIFORNIA LOS ANGELES
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：
https://reporter.nih.gov/project-details/7569493
关键词：
Address Agricultural Workers Agriculture Antigens Antiviral Agents Area Automobile Driving Autopsy Bangladesh Binding Biological Assay Biology Canada Carbohydrates Categories Cell Line Cell Surface Receptors Cell fusion Cell physiology Cell surface Cells Cellular Membrane Codon Nucleotides Collaborations Data Set Dendritic Cells Development Disease Outbreaks Emerging Communicable Diseases Encephalitis Endothelial Cells Ensure Funding Future GTP-Binding Proteins Galactose Binding Lectin Galectin 1 Giant Cells Glues Glycobiology Glycoproteins Grant Health Henipavirus Human Immune Immune response Immune system Immunology Infection Infectious Diseases Research Inflammation Inflammatory Interferons Lectin Life Livestock Lymphoid Tissue Malaysia Mediating Mediation Mediator of activation protein Membrane Fusion Membrane Microdomains Mutagenesis National Institute of Allergy and Infectious Disease National Institute of General Medical Sciences Natural Immunity Nipah Virus Oligosaccharides Paramyxoviridae Paramyxovirus Pathogenesis Pathologic Pathologist Patients Play Polysaccharides Principal Investigator Process Production Reagent Receptor Cell Research Research Personnel Role Singapore Structure T-Lymphocyte Testing Therapeutic Time Tissues Tropism Viral Virus Virus Diseases Virus Receptors Work base biodefense biosafety level 4 facility cell type cytokine env Glycoproteins experience glycoprotein G glycosylation in vivo inhibitor/antagonist innovation interdisciplinary approach lymph nodes member monocyte mortality mutant novel novel strategies particle pathogen receptor response virology virus envelope virus pathogenesis

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）是一种新兴的病毒性病原体，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，马来西亚和新加坡的农业工人感染NiV导致40%的死亡率和价值超过1亿美元的牲畜损失。NiV是副粘病毒新属的一员，对NiV的生物学或免疫反应知之甚少。