Virus-Host Immune System Interaction in a Ranavirus-Amphibian Model

蛙病毒-两栖动物模型中病毒-宿主免疫系统的相互作用

• 批准号: 0742711
• 负责人: Victor Chinchar
• 金额: $ 50万
• 依托单位: University of Mississippi Medical Center
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 2008
• 资助国家: 美国
• 起止时间: 2008-04-01 至 2013-03-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=0742711&HistoricalAwards=false
• 关键词: Virus; Host; Immune; System; Interaction

The goal of this project is to identify and characterize viral genes that control virulence and/or mediate immune evasion in the African clawed toad (Xenopus laevis) using frog virus 3 as a model. This project uses new technologies that selectively knock down the expression of specific viral genes, and generate mutant viruses in which specific candidate genes have been deleted. Mutant viruses will then be used to infect toads and the role of the candidate genes in disease and immune evasion determined. For example, it is likely that host has developed mechanisms to recognize and eliminate invading viruses, and that, in turn, viruses encode proteins designed to block those defenses. Such arms races are important in the evolution of both the host and the pathogen. If this is correct, then viral mutants where these countermeasures are deleted will fail to cause disease in infected animals. Successfully completed, this project will shed light on viral genes that control pathogenesis and, optimistically, reveal pathways used by the host to contain and eventually eliminate virus infections. In addition, this project may also uncover ways in which defects in amphibian immunity contribute to amphibian declines by making otherwise resistant animals susceptible to infection. Finally, this study may enhance understanding of the evolution of the immune system, and provide insight into ways to protect endangered amphibians from viruses and other pathogens. This project also has broader implications for the overall problem of worldwide decline in amphibian populations due in part to disease. It will provide training opportunities to a new generation of investigators in this field which is needed. Integral to the project is an outreach component to investigators at one of this nation?s Historically Black Colleges to enhance broadening participation in the field.

该项目的目标是使用青蛙病毒 3 作为模型，识别和表征非洲爪蟾（Xenopus laevis）中控制毒力和/或介导免疫逃避的病毒基因。该项目使用新技术选择性地敲低特定病毒基因的表达，并产生删除了特定候选基因的突变病毒。 然后，突变病毒将被用来感染蟾蜍，并确定候选基因在疾病和免疫逃避中的作用。例如，宿主很可能已经开发出识别和消除入侵病毒的机制，而反过来，病毒编码旨在阻止这些防御的蛋白质。这种军备竞赛对于宿主和病原体的进化都很重要。 如果这是正确的，那么删除这些对策的病毒突变体将不会在受感染的动物中引起疾病​​。 该项目成功完成后，将揭示控制发病机制的病毒基因，并乐观地揭示宿主用于遏制并最终消除病毒感染的途径。 此外，该项目还可能揭示两栖动物免疫缺陷导致两栖动物数量下降的方式，使原本具有抵抗力的动物容易受到感染。 最后，这项研究可能会增强对免疫系统进化的理解，并为保护濒危两栖动物免受病毒和其他病原体侵害的方法提供见解。 该项目还对部分由于疾病导致的全球两栖动物种群减少的总体问题具有更广泛的影响。 它将为该领域所需的新一代研究人员提供培训机会。 该项目的一个组成部分是向该国一所历史黑人大学的调查人员提供外展活动，以加强该领域的广泛参与。