Multi-level dynamics of viral co-infection

流行病学数据表明，在人类群体中共同传播的病毒以独特的方式相互作用 这可能导致复制、发病机制和传播动力学的改变，而不是 在隔离状态下运行。为了了解病毒混合感染在人群水平上的影响，关键是 剖析病毒在其共享宿主内的多个层次上的相互作用机制。中的一个系统 可以操纵哪些多个病毒和宿主对于模拟无关病毒的交互方式至关重要 以及这些相互作用如何改变感染的影响。这样做的长期目标是 研究旨在揭示病毒混合感染的特性，这些特性可以在其他系统中进行共性测试。这个 拟议研究的目标是建立一个易于处理的无脊椎动物病毒感染模型系统，并 共同感染，并开发数学模型来了解病毒如何相互作用以及它们的 寄主最终影响寄主的病理和种群动态。果蝇和相关病毒将是 用来检验中心假设，即与单一感染相比，联合感染导致非相加效应， 这些影响在不同的组织层面上是相互关联的。家蝇成虫口腔感染的研究 将用果蝇C病毒(DCV)和果蝇X病毒(DXV)来测试混合感染对病毒的影响 生长动态，宿主基因表达，病毒传播率，以及宿主人口统计学，包括繁殖力， 发育率和死亡率。目标1将通过量化病毒生长来关注分子间的相互作用 成人宿主转录组对单病毒和双病毒感染反应的动态和特征 苍蝇。在目标2中，混合感染对病毒的直接传播和环境传播的影响将是 下定决心。繁殖力、后代发育率和死亡率是人口的主要贡献者 动态，因此将是目标3的重点。了解混合感染如何改变苍蝇人口学将导致 共同传播病毒对受感染人群的长期影响的模拟。统计和数学 将使用三个目标内部和之间的建模来描述DCV和DXV之间的相互作用 在他们共享的主机中。这项研究将通过生成丰富的数据集来测试病毒联合感染的模型，从而推动这一领域的发展 通过建立一个易于处理的模型系统来研究病毒在多个地点的混合感染 组织层级。

Epidemiological data suggest that viruses that co-circulate within human populations interact in unique ways that can result in altered replication, pathogenesis, and transmission dynamics compared to how they would operate in isolation. In order to understand the effects of viral co-infection at population levels, it is critical to dissect the mechanisms of interaction between viruses at multiple levels within their shared host. A system in which multiple viruses and hosts can be manipulated is critical for modeling how unrelated viruses interact within their shared hosts and how these interactions alter the effects of infection. The long-term goal of this research is to uncover properties of viral co-infection that can be tested for generality in other systems. The objectives of the proposed study are to establish a tractable invertebrate model system of viral infection and co-infection, and to develop mathematical models to understand how viruses interact with each other and their host to ultimately affect the host pathology and population dynamics. Drosophila and associated viruses will be used to test the central hypothesis that co-infection results in non-additive effects relative to single infections, and that these effects are correlated at different levels of organization. Oral infection of adult flies with Drosophila C virus (DCV) and Drosophila X virus (DXV) will be used to test the effects of co-infection on viral growth dynamics, host gene expression, viral transmission rates, and host demography, including fecundity, developmental rate, and mortality. Aim 1 will focus on molecular interactions, by quantifying viral growth dynamics and characterizing the host transcriptome in response to single and dual virus infections in adult flies. In Aim 2, the effects of co-infection on both direct and environmental transmission of the viruses will be determined. Fecundity, offspring developmental rate, and mortality are major contributors to population dynamics and will thus be the focus of Aim 3. Understanding how co-infection alters fly demography will lead to modeling of long-term impacts of co-circulating viruses in infected populations. Statistical and mathematical modeling within and between the three aims will be used to describe the interactions between DCV and DXV within their shared host. This study will advance the field by generating rich datasets to test models of viral co- infection and by establishing a tractable model system for the study of viral co-infection at multiple organizational levels.