Retrocyclin reinforcement of pulmonary defenses against viral aerosols

逆环素增强肺部针对病毒气溶胶的防御能力

基本信息

批准号：
7229818
负责人：
ROBERT IRVING LEHRER
金额：
$ 11.21万
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：
2006
资助国家：
美国
起止时间：
2006-02-15 至 2009-01-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/7229818
关键词：
Abattoirs Aerosols Air Air Sacs Alphavirus Anti-Bacterial Agents Antifungal Agents Antiviral Agents Arenaviridae Baculoviruses Behavior Binding Biological Assay Biological Models Bioterrorism Bos taurus Breathing C-Type Lectins Carbohydrates Cattle Cell fusion Cells Cercopithecidae Collagen Collectins Coronaviridae Defensins Drug Formulations Epithelial Epithelial Cells Exposure to Family Family suidae Film Flaviviridae Genes Glycoproteins Gorilla gorilla HIV-1 Head Health Herpes Simplex Infections Human In Vitro Influenza Language Lectin Leukocytes Lipids Liquid substance Lung Mannose Binding Lectin Membrane Mission Mutation Nonsense Codon Orthomyxoviridae Pan Genus Pan troglodytes Paramyxoviridae Paramyxovirus Peptide Signal Sequences Peptide Synthesis Peptides Phase Phospholipids Plasma Pongidae Poxviridae Property Proteins Pseudogenes Psychological reinforcement Pulmonary Surfactant-Associated Protein A Pulmonary Surfactant-Associated Protein B Pulmonary Surfactant-Associated Protein D Pulmonary Surfactants Pulmonary alveolar structure Research Design Serum Serum Proteins Severe Acute Respiratory Syndrome Solid Standards of Weights and Measures Structure Surface Surface Plasmon Resonance System Tacaribe virus Testing Togaviridae Vaccinia Vesicle Viral Virus Virus Diseases West Nile virus Yellow fever virus alpha-Fetoproteins analog base clinically significant crosslink cytotoxicity fetal milligram monolayer nonhuman primate particle prototype response retrocyclin surfactant

项目摘要

DESCRIPTION (provided by applicant): Introduction: In addition to the a and ¿ defensins produced by human leukocytes and epithelial cells, many nonhuman primates produce ?-defensins, representing a third defensin subfamily. ?-defensins lack potent antibacterial or antifungal activity, but have broad antiviral properties. Retrocyclins are ?-defensins whose structures are based on the sequences of expressed (but untranslated) human ?-defensin pseudogenes. Broad, Long term objectives: To use retrocyclins to enhance pulmonary defenses to viral aerosols. Specific aims. 1. To test retrocyclins against potential viral bioterrorism agents, including Influenza A and B (Orthomyxoviridae), HPIV3 (Paramyxoviridae), West Nile and Yellow Fever virus (Flaviviridae) SARS-CoV (Coronaviridae), Vaccinia (Poxviridae), VEE, an alphavirus (Togaviridae), and Tacaribe virus (Arenaviridae) 2. To examine the interactions of retrocyclins with surfactant proteins SP-A and SP-D. 3. To test the effects actions of RC2 on monolayers and bilayers of pulmonary surfactant phospholipids. Research Design. Retrocyclin-2 (RC-2) and selected analogs will be prepared by solid phase peptide synthesis. Viruses will be tested in vitro by standard plaque reduction and CPE reduction assays. The effects of retrocyclins on the integrity of surfactant phospholipid films will be tested in monolayer systems by using a Langmuir-Blodgett trough, and in bilayer systems by using vesicles composed of surfactant lipids and associated surfactant proteins SP-B and SP-C. Binding of retrocyclins to SP-A and SP-D will be studied by surface plasmon resonance. Effects of retrocyclins on the intrinsic antiviral activity of SP-A and SP-D (and vice versa) will be studied using proteins purified from abattoir-obtained porcine lungs in standard plaque reduction and CPE reduction assays. Health relatedness and Agency Mission. This application is in direct response to PA 04-119. Lay language summary. Many natural viral infections begin with exposure to air that contains viruses. Viral aerosols may also allow bioterrorists to deliver incapacitating viruses. We propose to test the activity of retrocyclins (newly discovered antiviral peptides) against potential viral bioterrorism agents, and to determine their biocompatability with ELF-the thin fluid layer that covers the surface of the pulmonary air sacs.

描述（应用程序提供）：简介：除了由人白细胞和上皮细胞产生的A和«防御素外，许多非人类素质还会产生？-Defensin，代表第三个防御素亚科。 - 防御素缺乏潜在的抗菌或抗真菌活性，但具有广泛的抗病毒特性。倒角蛋白是？ - 二防御素的结构是基于表达（但未翻译的）人类的序列？-Defensin pseudogenes。宽阔的长期目标：使用折叠蛋白来增强病毒气溶胶的肺部防御。具体目标。 1。针对潜在的病毒生物恐怖剂进行测试，包括流感A和B（Orthomyxoviridae），HPIV3（Paramyxoviridae），西尼罗河和黄热病病毒（Flaviviviridae）SARS-COV（coronaviridae），coronaviridae），疫苗（poxviridae），alphaviridae，veirutae，and and and and and and and and and veirutae and and and and antaviridae and veirutae and and and。塔卡里贝病毒（Arenaviridae）2。检查倒角蛋白与表面活性剂蛋白SP-A和SP-D的相互作用。 3。测试RC2对肺表面活性剂磷脂的单层和双层的作用。研究设计。腹循环2（RC-2）和选定的类似物将通过固相肽合成制备。病毒将在体外通过标准斑块减少和减少CPE测定进行测试。逆转录蛋白对表面活性剂磷脂膜完整性的影响将在单层系统中使用Langmuir-Blodgett Troough以及在双层系统中使用由表面活性剂脂质和相关的表面活性剂蛋白SP-B和SP-C和SP-C和SP-C进行测试。返回周期蛋白与SP-A和SP-D的结合将通过表面等离子体共振进行研究。返回周期蛋白对SP-A和SP-D（反之亦然）内在抗病毒活性的影响将使用在标准的斑块还原和CPE减少分析中纯化的蛋白质纯化的蛋白质。健康相关性和代理任务。此应用程序直接响应PA 04-119。外行语言摘要。许多天然病毒感染始于暴露于含有病毒的空气。病毒气溶胶还可以使生物恐怖分子传递无行为能力的病毒。我们建议测试逆转录蛋白（新发现的抗病毒辣椒）对潜在的病毒生物恐怖剂的活性，并确定其与精灵 - 薄薄的流体层的生物相容性，覆盖肺囊的表面。