Sigma virus in Drosophila: a model system for the evolution of virulence

果蝇中的西格玛病毒：毒力进化的模型系统

• 批准号: 7877149
• 负责人: Marta L Wayne
• 金额: $ 4.41万
• 依托单位: UNIVERSITY OF FLORIDA
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-05-01 至 2013-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7877149
• 关键词: Affect; Animal Model; Animals; Attenuated; Biological Models; Caring; Cell Culture Techniques; Communicable Diseases; Containment; Culicidae; Data; Demography; Dengue; Disease; Drosophila genus; Drosophila melanogaster; Ecology; Elements; Epidemiology; Equilibrium; Equine Encephalomyelitis; Evolution; Generations; Genes; Genetic; Genetic Models; Genomics; Health; Human; Infection; Insect Vectors; Insecta; Knowledge; Literature; Modeling; Molecular Genetics; Mothers; Natural History; Nature; Organism; Outcome; Parasites; Parents; Population; Population Genetics; Population Sizes; Property; RNA Viruses; Reading; Relative (related person); Resources; Rhabdoviridae; Rivers; Sampling; Scientist; Serial Passage; Shapes; Siblings; Side; Source; System; Technology; Test Result; Testing; Time; Training; Vertical Disease Transmission; Viral; Viral Genome; Viremia; Virulence; Virulent; Virus; West Nile virus; Work; Yellow Fever; attenuation; data modeling; disorder control; egg; fitness; fly; genome sequencing; in vivo; male; microbial; novel; offspring; pathogen; public health relevance; research study; response; simulation; theories; tool; trait; transmission process

DESCRIPTION (provided by applicant): Many emerging viral pathogens are vertically transmitted in dipterans (dengue, West Nile, etc.). Understanding the genetic and evolutionary mechanisms that determine the virulence of vertically transmitted parasites is central to predicting and controlling these diseases. We will develop a model system combining theory with data for sigma virus, a vertically transmitted Rhabdovirus, in Drosophila melanogaster. The sigma virus-D. melanogaster system, with its ease of husbandry, extensive natural history, and wealth of genomic tools, is a superb model system for exploring 1) the evolution of virulence in general and 2) contrasting uniparentally vs. biparentally transmitted viruses in particular. Virulence, the damage done to the host, is a constantly evolving property in both established and emerging diseases; using an in vivo, animal model system to test the generality of results of virulence evolution from microbial or cell culture serial passage experiments is an essential initial step toward predicting and ultimately managing such evolutionary changes. Vertical transmission can maintain dangerous emerging viruses in their insect vector populations; information from a model system can help us predict and manage these viral reservoirs. We utilize a two-pronged experimental evolution study of sigma, an RNA virus, in intact animal hosts. First, we create replicated, artificial host shifts between D. melanogaster, in which infection is endemic; and in D. simulans, the host's sibling species, in which there is no infection. We thereby test predictions from microbial and cell culture serial passage experiments, which have not been evaluated before in an intact animal to the best of our knowledge. Specifically, we ask whether or not virulence necessarily increases with host shift; and whether or not "shifted" virus is necessarily attenuated (less virulent) in the original host. Next, we manipulate viremia via artificial selection in D. melanogaster, contrasting outcomes under biparental vs. uniparental transmission, to test whether or not rates of evolution of virulence are dependent on precise mode of vertical transmission as predicted by some theory. In both projects, we also explicitly quantify the relationship between viremia, virulence, and male transmission. We also characterize genomic outcomes and the source and nature of adaptations resulting from experimental evolution via whole-genome sequencing. The theoretical components of the project use a variety of modeling tools ranging from simple genetic models to simulations to understand conditions governing the rate of the evolution of virulence. We provide both a general theory aim, incorporating elements from evolutionary ecology and population genetics; and a second aim connecting data from this project with existing theory on the evolution of virulence. Our experiments and theory will provide a generalized, integrated understanding of evolution of virulence; and represent a significant step forward in our understanding of viral evolution as relevant to human health by testing results from existing theory and from microbial and cell culture in an intact, animal system. PUBLIC HEALTH RELEVANCE: This project aims to understand how vertically transmitted viruses (i.e., viruses transmitted from parents to offspring) become more or less harmful (i.e., change their virulence) and how they may change from one host to another. Data and models from this study will help scientists understand better how the virulence of human infectious diseases changes over time, how emerging diseases arise, and how we may be able to predict and control these changes; results will also help explain how insect-borne viruses such as West Nile and Dengue fever can persist in insect populations in the absence of human contact.

描述（由申请人提供）：许多新出现的病毒病原体在双翅目动物（登革热、西尼罗河等）中垂直传播。了解决定垂直传播寄生虫毒力的遗传和进化机制对于预测和控制这些疾病至关重要。我们将开发一个将理论与数据相结合的模型系统，用于黑腹果蝇中的西格玛病毒（一种垂直传播的弹状病毒）。西格玛病毒-D。黑腹果蝇系统具有易于饲养、广泛的自然历史和丰富的基因组工具，是一个极好的模型系统，可用于探索 1) 一般毒力的进化和 2) 特别是单亲传播病毒与双亲传播病毒的对比。毒力，即对宿主造成的损害，是既定疾病和新发疾病不断演变的特性；使用体内动物模型系统来测试微生物或细胞培养连续传代实验毒力进化结果的普遍性，是预测和最终管理此类进化变化的重要第一步。垂直传播可以在昆虫媒介种群中维持危险的新兴病毒；来自模型系统的信息可以帮助我们预测和管理这些病毒库。我们在完整的动物宿主中对 sigma（一种 RNA 病毒）进行了双管齐下的实验进化研究。首先，我们在黑腹果蝇之间创建复制的人工宿主转移，其中感染是地方性的；以及在宿主的近亲物种 D. simulans 中，没有受到感染。因此，我们测试了微生物和细胞培养连续传代实验的预测，据我们所知，这些预测之前尚未在完整的动物中进行过评估。具体来说，我们想知道毒力是否必然随着宿主的转移而增加？以及“转移的”病毒在原始宿主中是否必然减毒（毒性较低）。接下来，我们通过黑腹果蝇的人工选择来操纵病毒血症，对比双亲和单亲传播下的结果，以测试毒力进化速度是否依赖于某些理论预测的精确的垂直传播模式。在这两个项目中，我们还明确量化了病毒血症、毒力和男性传播之间的关系。我们还通过全基因组测序描述了实验进化产生的基因组结果以及适应性的来源和性质。该项目的理论部分使用各种建模工具，从简单的遗传模型到模拟，以了解控制毒力进化速率的条件。我们提供了一个总体理论目标，结合了进化生态学和群体遗传学的要素；第二个目标是将该项目的数据与现有的毒力进化理论联系起来。我们的实验和理论将为毒力进化提供一个普遍的、综合的理解；通过测试现有理论以及完整动物系统中微生物和细胞培养的结果，代表我们在理解病毒进化与人类健康相关方面向前迈出了重要一步。公共卫生相关性：该项目旨在了解垂直传播的病毒（即从父母传播给后代的病毒）如何变得或多或少有害（即改变其毒力）以及它们如何从一个宿主转移到另一个宿主。这项研究的数据和模型将帮助科学家更好地了解人类传染病的毒力如何随时间变化、新发疾病如何出现以及我们如何能够预测和控制这些变化；研究结果还将有助于解释西尼罗河病毒和登革热病毒等虫媒病毒如何在没有人类接触的情况下在昆虫种群中持续存在。