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

本项目的目标是以青蛙病毒3型为模型，在非洲爪蛙(Xenopus Laevis)中识别和表征控制毒力和/或介导免疫逃避的病毒基因。该项目使用新技术，选择性地抑制特定病毒基因的表达，并产生特定候选基因已被删除的突变病毒。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了识别和消除入侵病毒的机制，反过来，病毒编码了旨在阻止这些防御的蛋白质。这种军备竞赛在宿主和病原体的进化中都很重要。如果这是正确的，那么这些对策被删除的病毒突变将不会在受感染的动物中引起疾病。该项目成功完成后，将阐明控制发病机制的病毒基因，并乐观地揭示宿主用来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通过使原本具有抵抗力的动物更容易受到感染而导致两栖动物衰退的方式。最后，这项研究可能会加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洞察力。该项目对全球两栖动物数量下降这一整体问题也有更广泛的影响，这部分是由于疾病造成的。它将为需要的这一领域的新一代调查人员提供培训机会。该项目不可或缺的一部分是向这个国家之一的研究人员--S历史上的黑人学院--提供一个外展部分，以加强在该领域的广泛参与。

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.