The Role of a Host ion Pump in RNA Virus Recombination

病毒进化速度极快，极大地影响了宿主与病毒的相互作用。病毒的进化通常是由基因重组驱动的，这一过程使病毒能够克服免疫力，感染新的宿主物种并改变所有类型的生物体的疾病症状。病毒重组也是新病毒出现的主要因素，对我们的社会构成持续威胁。因此，研究宿主对病毒重组过程的影响对于解开目前人们知之甚少的病毒进化至关重要。该项目重点研究最近发现的影响番茄浓密矮化病毒 RNA 重组的关键宿主因子。宿主因子是 Pmr1p Ca2 /Mn2 离子泵，它是一种普遍存在的保守蛋白，在人类遗传疾病（例如 Hailey-Hailey 病和 Darier 病）中发挥着关键作用。为了表征 Pmr1p 在病毒 RNA 重组中的作用，研究人员将使用可用于植物和酵母（模型宿主）的先进遗传学工具，并结合生化方法。这项研究预计将在病毒重组方面带来重要的新发现，并为宿主在病毒进化和病毒与宿主相互作用中的作用贡献关键知识。更广泛的影响：该研究有望通过在病毒重组/进化、宿主与病毒相互作用和新病毒的出现等领域取得突破性成果，造福社会。当前抗病毒方法的主要限制是，由于病毒快速进化，它们可能很快失效。更好地了解病毒 RNA 重组将对我们开发更好、更持久的抗病毒策略的能力产生巨大影响。教育部分：高中生和本科生将积极参与研究者实验室的研究。

Host - virus interactions are greatly affected by the exceptionally rapid rate of virus evolution. Evolution of viruses is frequently driven by genetic recombination, a process that allows viruses to overcome immunity, to infect new host species and change disease symptoms in all types of living organisms. Virus recombination is also a major factor in emergence of new viruses, which is a continuing threat to our society. Therefore, studies on the effect of the host on the viral recombination process are critical to unravel virus evolution, which is currently poorly understood. This project focuses on a recently discovered key host factor affecting RNA recombination in Tomato bushy stunt virus. The host factor is Pmr1p Ca2+/Mn2+ ion-pump, which is a ubiquitous and conserved protein playing critical roles in human genetic diseases, such as Hailey-Hailey Disease and Darier Disease. In order to characterize the role of Pmr1p in viral RNA recombination, the investigator will use advanced genetics tools available for plant and yeast, which is a model host, in combination with biochemical approaches. This research is expected to lead to important new discoveries in viral recombination and contribute key knowledge to the role of the host in virus evolution and virus-host interactions.Broader impact: The research holds promise of benefiting society by leading to groundbreaking results in the area of virus recombination/evolution, host-virus interaction and the emergence of new viruses. The major limitation of current antiviral methods is that they could quickly become ineffective due to rapid virus evolution. Better understanding of viral RNA recombination will have tremendous impact on our abilities to develop better, longer lasting antiviral strategies. Education component: High school and undergraduate students will actively participate in research in the investigator's laboratory.