CAREER: Population Dynamics and Evolutionary Ecology of Viral Emergence

新的病毒偶尔会出现在人群中，并可能严重影响公共卫生，艾滋病毒的大流行就是明证。然而，很少有人知道的生态和进化因素，影响人口动态的新兴病毒。部分问题在于，由于时间、空间和伦理的限制，很难利用致病病毒及其动物宿主进行实验研究。 细菌病毒及其细菌宿主提供了一个易于操作的模型系统，以研究大的病毒和宿主种群在短时间尺度上的动态。该提案具体阐述了关于病毒进入新宿主类型的几个突出假设。第一个目的是确定初始病毒适应性是否与新宿主出现的概率呈正相关。第二个目的是确定病毒适应是否在混合宿主社区相比，包含一个单一的主机类型的社区增强。第三个目标是确定感染不同宿主的病毒种群之间的基因流动是否会增强适应性进化。第四个目的是探讨翻译顺应的意义（即，噬菌体密码子选择的进化以匹配宿主tRNA丰度）。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真实，并提高我们识别和应对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.