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:
- 金额:$ 11.21万
- 依托单位:
- 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:
- 关键词:AbattoirsAerosolsAirAir SacsAlphavirusAnti-Bacterial AgentsAntifungal AgentsAntiviral AgentsArenaviridaeBaculovirusesBehaviorBindingBiological AssayBiological ModelsBioterrorismBos taurusBreathingC-Type LectinsCarbohydratesCattleCell fusionCellsCercopithecidaeCollagenCollectinsCoronaviridaeDefensinsDrug FormulationsEpithelialEpithelial CellsExposure toFamilyFamily suidaeFilmFlaviviridaeGenesGlycoproteinsGorilla gorillaHIV-1HeadHealthHerpes Simplex InfectionsHumanIn VitroInfluenzaLanguageLectinLeukocytesLipidsLiquid substanceLungMannose Binding LectinMembraneMissionMutationNonsense CodonOrthomyxoviridaePan GenusPan troglodytesParamyxoviridaeParamyxovirusPeptide Signal SequencesPeptide SynthesisPeptidesPhasePhospholipidsPlasmaPongidaePoxviridaePropertyProteinsPseudogenesPsychological reinforcementPulmonary Surfactant-Associated Protein APulmonary Surfactant-Associated Protein BPulmonary Surfactant-Associated Protein DPulmonary SurfactantsPulmonary alveolar structureResearch DesignSerumSerum ProteinsSevere Acute Respiratory SyndromeSolidStandards of Weights and MeasuresStructureSurfaceSurface Plasmon ResonanceSystemTacaribe virusTestingTogaviridaeVacciniaVesicleViralVirusVirus DiseasesWest Nile virusYellow fever virusalpha-Fetoproteinsanalogbaseclinically significantcrosslinkcytotoxicityfetalmilligrammonolayernonhuman primateparticleprototyperesponseretrocyclinsurfactant
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(由申请人提供):简介:除了人白细胞和上皮细胞产生的α和β防御素外,许多非人灵长类动物还产生?防御素,代表第三个防御素亚家族。?-防御素缺乏有效的抗细菌或抗真菌活性,但具有广泛的抗病毒特性。逆转录病毒是什么?防御素的结构是基于表达(但未翻译)的人类?防御素假基因广泛的长期目标:使用逆转录病毒素增强肺部对病毒气溶胶的防御。具体目标。1.检测逆转录病毒对潜在病毒生物恐怖因子的作用,包括甲型和B型流感病毒(正粘病毒科)、HPIV 3(副粘病毒科)、西尼罗河和黄热病毒(黄病毒科)、SARS-CoV(冠状病毒科)、牛痘病毒(痘病毒科)、VEE、一种甲病毒(披膜病毒科)和塔卡里布病毒(沙粒病毒科)2。目的:研究逆转录细胞周期素与表面活性蛋白SP-A和SP-D的相互作用。3.测试RC 2对肺表面活性物质磷脂单层和双层的影响。研究设计。逆转录细胞周期蛋白-2(RC-2)和选定的类似物将通过固相肽合成制备。将通过标准空斑减少和CPE减少试验在体外检测病毒。将在单层系统中通过使用Langmuir-Blodgett槽,并在双层系统中通过使用由表面活性剂脂质和相关表面活性剂蛋白SP-B和SP-C组成的囊泡,测试retrocyclins对表面活性剂磷脂膜完整性的影响。将通过表面等离子体共振研究逆转录细胞周期蛋白与SP-A和SP-D的结合。将使用从屠宰场获得的猪肺中纯化的蛋白质,在标准空斑减少和CPE减少测定中研究逆转录病毒素对SP-A和SP-D的内在抗病毒活性的影响(反之亦然)。健康相关性和机构使命。本申请是对PA 04-119的直接回应。Lay language summary.许多自然病毒感染开始与暴露于空气中含有病毒。病毒气溶胶也可能使生物恐怖分子能够传播使人丧失能力的病毒。我们建议测试的活性retrocyclins(新发现的抗病毒肽)对潜在的病毒生物恐怖剂,并确定其与ELF的生物相容性薄液层,覆盖在肺气囊的表面。
项目成果
期刊论文数量(0)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
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ROBERT IRVING LEHRER其他文献
ROBERT IRVING LEHRER的其他文献
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{{ truncateString('ROBERT IRVING LEHRER', 18)}}的其他基金
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
- 批准号:
7012946 - 财政年份:2006
- 资助金额:
$ 11.21万 - 项目类别:
Theta-defensins Novel HIV-1 Uptake Inhibitors
Theta-防御素新型 HIV-1 摄取抑制剂
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7052112 - 财政年份:2005
- 资助金额:
$ 11.21万 - 项目类别:
Theta-defensins Novel HIV-1 Uptake Inhibitors
Theta-防御素新型 HIV-1 摄取抑制剂
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7217903 - 财政年份:2005
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$ 11.21万 - 项目类别:
Theta-defensins Novel HIV-1 Uptake Inhibitors
Theta-防御素新型 HIV-1 摄取抑制剂
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6892009 - 财政年份:2005
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BIACORE 3000 SPR INSTRUMENT: INFECTIOUS DISEASE
BIACORE 3000 SPR 仪器:传染病
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6973318 - 财政年份:2004
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Theta-防御素:新型 HIV-1 摄取抑制剂
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