CAREER: Population Dynamics and Evolutionary Ecology of Viral Emergence

新病毒偶尔出现在人类群体中，并可能严重影响公共卫生，艾滋病毒的大流行传播就是明证。然而，对影响新出现病毒种群动态的生态和进化因素知之甚少。部分问题是，由于时间、空间和伦理的限制，使用致病病毒及其动物宿主进行实验研究是困难的。细菌病毒及其宿主提供了一个易于操作的模型系统来研究大病毒和宿主种群在短时间尺度上的动态。该提案特别提出了关于病毒出现在新的宿主类型中的几个突出假设。第一个目标是确定新宿主上的初始病毒适合度是否与出现的概率呈正相关。第二个目标是确定与包含单一宿主类型的社区相比，混合宿主社区的病毒适应能力是否得到加强。第三个目标是确定感染不同宿主的病毒群体之间的基因流动是否增强了适应性进化。第四个目的是研究翻译适应(即噬菌体密码子使用的进化以匹配宿主tRNA丰度)在病毒出现中的意义。这些实验共同构成了研究病毒出现的最全面的实验方法之一。这项工作的成功完成可能会使病毒出现的模型更加现实，并增强我们识别和对抗潜在危险病毒的能力。

New viruses occasionally appear in human populations and can significantly affect public health as evidenced by the pandemic spread of HIV. However, little is known of the ecological and evolutionary factors that impact the population dynamics of emerging viruses. Part of the problem is that it is difficult to conduct experimental studies using pathogenic viruses and their animal hosts because of time, space and ethical constraints. Bacterial viruses and their bacterial hosts provide an easy to manipulate model system to study the dynamics of large virus and host populations over a short time scale. The proposal specifically addresses several prominent hypotheses regarding the emergence of viruses into new host types. The first aim is to ascertain whether initial virus fitness on the novel host is positively correlated with the probability of emergence. The second aim is to determine whether virus adaptation is enhanced in mixed host communities as compared to communities containing a single host type. The third aim is to establish whether gene flow between virus populations infecting different hosts enhances adaptive evolution. The fourth aim is to investigate the significance of translational adaptation (i.e., evolution of phage codon usage to match host tRNA abundance) in viral emergence. Together these experiments constitute one of the most comprehensive experimental approaches to the study of virus emergence attempted. Successful completion of the work may allow more realistic models of virus emergence and enhance our ability to identify and counteract potentially dangerous viruses.