RAPID: Ebola virus population structure, genetic diversity and evolution

这个NSF RAPID项目支持开发一个实验和计算平台，使研究人员能够研究埃博拉病毒基因组如何随时间进化或变化，以及它如何从蝙蝠传播到人类宿主。埃博拉病毒是一种RNA病毒。像其他RNA病毒一样，它是一组相互关联但又截然不同的病毒。据认为，这种多样性使病毒能够适应环境变化。对在人类和蝙蝠细胞中进化的病毒种群进行深度测序，将有助于更好地了解病毒的进化，并确定促进适应和导致传播和疾病的因素。了解病毒的进化将使研究人员能够更好地控制未来的埃博拉病毒爆发，并开发更好的预防疫苗。RNA病毒快速进化的极端能力正在成为致病性和毒力的关键决定因素之一，也是新病毒株迅速出现和对抗病毒药物产生耐药性的驱动力。尽管它很重要，但目前很少有概念性和实验性的工具来研究病毒的进化及其与发病机制的关系。在该RAPID奖中，PI建议审查埃博拉病毒的进化及其与人类和蝙蝠细胞复制的关系。该方法将结合病毒学实验、新的基因组分析方法和计算建模，以揭示埃博拉病毒进化的基本原理。研究人员将解决有关埃博拉病毒在人类和蝙蝠之间循环规律的基本问题，包括：1)是什么决定了病毒种群的多样性：是突变的产生速度还是病毒种群的选择压力？2)特定病毒种群在不同环境下适应的潜在遗传结构是什么？这些结构在不同环境条件下的动态如何？3)病毒准种多样性、适应度和适应性之间的关系是什么？这些实验的结果将为了解埃博拉病毒种群的进化如何决定感染的结果开辟道路。这些方法将对疫苗开发、预测和控制埃博拉病毒爆发的能力以及对RNA基因组快速进化的理解产生重大影响。

This NSF RAPID project supports the development of an experimental and computational platform that allows researchers to examine how the Ebola virus genome evolves or changes with time and as it moves from bat to human hosts. The Ebola virus is an RNA virus. Like other RNA viruses, it exists as a diverse collection of related, but distinct individual viruses. It is thought that this diversity allows the virus to adapt to environmental changes. The deep sequencing of a virus population as it evolves in human and bat cells will allow for a better understanding viral evolution and identify factors that facilitate adaptation and lead to spread and disease. Understanding virus evolution will better enable researchers to control future Ebola virus outbreaks and develop better vaccines for its prevention.The extreme capacity of RNA viruses for rapid evolution is emerging as one of the key determinants of pathogenicity and virulence, as well as the driving force underlying the rapid emergence of new viral strains and the development of resistance to antivirals. Despite its importance, few conceptual and experimental tools are currently available to study viral evolution and its relationship to pathogenesis. In this RAPID award, the PI proposes to examine Ebola virus evolution and its relationship to replication in human and bat cells. The approach will combine virological experiments, novel genome analysis approaches and computational modeling to uncover basic principles of Ebola virus evolution. The investigators will address fundamental questions about the rules that govern Ebola cycling between human and bats including: 1) what determines the diversity of the virus population: the rate of generation of mutations or the selective pressures on the virus population? 2) what are the potential genetic structures adapted by a given virus population under different environments and how dynamic are these structures under diverse environmental conditions? 3) What is the relationship between viral quasispecies diversity, fitness and adaptability? The results from these experiments will open the way to understand how the evolution of Ebola virus populations determines the outcome of infection. These approaches will have a major impact in vaccine development, on the ability to anticipate and control Ebola virus outbreaks, and on the understanding of rapid evolution of RNA genomes.