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

本项目的目标是鉴定和表征控制非洲爪蟾毒力和/或介导免疫逃避的病毒基因，以青蛙病毒3为模型。该项目使用新技术，选择性地降低特定病毒基因的表达，并产生突变病毒，其中特定的候选基因已被删除。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，宿主可能已经发展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无法在受感染的动物中引起疾病。成功完成后，该项目将揭示控制发病机制的病毒基因，并乐观地揭示宿主控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途径，使原本具有抵抗力的动物容易受到感染。最后，这项研究可以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的侵害提供见解。该项目还对部分由于疾病导致的全球两栖动物数量下降的整体问题具有更广泛的影响。它将为这一领域所需要的新一代研究人员提供培训机会。这个项目的组成部分是向这个国家的调查人员提供外展服务？s历史上的黑人学院，以加强扩大在该领域的参与。

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.