The evolutionary and mechanistic basis of virus host shifts: A Staphylococcaceae-phage system to investigate patterns of virus infectivity and evoluti

病毒宿主转移的进化和机制基础：一种研究病毒感染性和跨宿主物种进化模式的葡萄球菌-噬菌体系统病毒宿主转移-病毒从一个宿主物种跳到另一个宿主物种-是新兴传染病的主要来源。例如，埃博拉病毒、艾滋病病毒和SARS冠状病毒都是从其他物种传染给人类的。尽管新出现的病毒性疾病很重要，但我们对决定病毒感染某些宿主而不感染其他宿主的能力的因素，或者病毒如何在不同宿主中进化的理解有限（Longdon et al.2014，https：//doi.org/10.1371/journal.ppat.1004395）。了解这些过程对于预测未来疾病将在何时何地出现至关重要。基础病毒是新出现的传染病的主要原因，通常感染多个宿主物种的RNA病毒被认为是最有可能出现的。此外，宿主转移似乎最经常发生在密切相关的宿主物种之间。然而，这些假设的证据主要来自比较数据（即没有实验操作的观察）。因此，它们为我们指出了有趣的研究领域，但无法梳理解释观察到的模式的复杂过程。实验研究强调了一些重要的宿主-病毒相互作用，这些相互作用导致成功的宿主转移（例如细小病毒从猫到狗（Parrish et al. 2008 http://doi.org/ MMBR.00004-08）），但大多数这些研究仅限于两个宿主系统。因此，使用广泛的宿主物种，在其相关性不同的实验研究是必不可少的，使广泛适用的结论。我们之前的工作已经使用了多达50种果蝇及其天然存在的RNA 4 / 15病毒（Longdon et al. 2011 and 2015 https://doi.org/10.1371/journal.ppat.1002260 and https：//doi.org/10.1371/journal.ppat.1004728）来检查宿主转移（视频见www.goo.gl/sXBiv5）。通过使用大量不同的宿主物种，我们能够找到适用于不同相关性的宿主物种的一般模式。本项目将使用细菌病毒系统研究病毒进化对宿主转移的后果，从而提出有关疾病出现的基本问题。我们将使用一组超过50种不同的葡萄球菌和广泛的宿主范围的噬菌体。这个模型提供了一个独特的机会来进行实验，这在脊椎动物系统中是不可能的，关键是将使我们能够使用实验进化来询问有关病原体宿主转移的基本问题。这个跨学科的项目整合了病原体宿主转移（Ben Longdon，埃克塞特）和细菌-噬菌体协同进化（安格斯Buckling，埃克塞特）的专业知识。

The evolutionary and mechanistic basis of virus host shifts: A Staphylococcaceae-phage system to investigate patterns of virus infectivity and evolution across host speciesVirus host shifts - where a virus jumps from one host species to another - are a major source of emerging infectious diseases. For example, Ebola, HIV and SARS coronavirus have all jumped into humans from otherspecies. Despite the importance of emerging viral diseases, we have a limited understanding about what determines the ability of a virus to infect some groups of hosts but not others, or how viruses will evolve in different hosts (Longdon et al. 2014, https://doi.org/10.1371/journal.ppat.1004395). Understanding these processes is vital to predict when and where diseases will emerge in the future.BACKGROUNDViruses are disproportionally responsible for emerging infectious diseases, with RNA viruses that normally infect multiple host species considered the most likely to emerge. Additionally, host shifts appear to occur mostoften between closely related host species. However, evidence for these hypotheses largely come from comparative data (i.e. observations with no experimental manipulation). Therefore, they point us toward interesting areas for investigation, but cannot tease apart the complex processes explaining the observed patterns.Experimental studies have highlighted some of the important host-virus interactions that result in successful host shifts (e.g. parvoviruses from cats to dogs (Parrish et al. 2008 http://doi.org/ MMBR.00004-08) but the majority of these studies have been limited to two host systems. Therefore, experimental studies using a wide breadth of host species that vary in their relatedness are essential to make broadly applicable conclusions. Our previous work has used up to 50 species of Drosophila, and their naturally occurring RNA 4 / 15 viruses (Longdon et al. 2011 and 2015 https://doi.org/10.1371/journal.ppat.1002260 and https://doi.org/10.1371/journal.ppat.1004728) toexamine host shifts (video here www.goo.gl/sXBiv5). By using a large number of different host species we are able to find general patterns that apply across host species with varying relatedness.This project will ask fundamental questions about disease emergence using a bacteriavirus system to study the consequences of virus evolution on host shifts. We will use a panel of over 50 different Staphylococcusspecies and a broad host range bacteriophage. This model offers a unique opportunity to perform experiments that would not be possible in a vertebrate-system, and critically will allow us to use experimental evolution to ask fundamental questions about pathogen host shifts. This interdisciplinary project integrates expertise on pathogen host shifts (Ben Longdon, Exeter) and bacteria-phage coevolution (Angus Buckling, Exeter).