High-density DNA microarrays offer an unparalleled view of the transcriptional events that underlie the host response to pathogens, providing a quantitative description of the behavior of tens of thousands of genes. In recent years, microarrays have been widely used to analyze the alteration of gene expression in host cells after infection with both animal [e.g., [8] [9] [10] [11] [12] [13] and plant [e.g., [14] [15] [16] [17] [18] viruses. However, a common drawback of these previous studies is that experiments were either done in cell cultures [8] [9] [10] [11] [12] [13] , which always represent an artificial and oversimplified environment, or using host-virus pairs whose previous evolutionary history of association is unknown and the degree of impact of abiotic environmental factor uncontrolled [14, 17] . Therefore, the relevance of these studies and, more importantly, their evolutionary implications for the problem of emergent infectious diseases, are rather limited. In the following, the results from an experiment simulating the emergence of a plant virus that crossed the species barrier and is horizontally spreading on a population of partially-susceptible hosts are reported. Evolutionary changes in viral genome and phenotypic properties and, more importantly, in the way it interacts with its host's transcriptome are the focus of the study.