A comprehensive physical interaction map between the Turnip mosaic potyvirus and Arabidopsis thaliana proteomes

Abstract Viruses are obligate intracellular parasites that have co-evolved with their hosts to establish an intricate network of protein-protein interactions. Yet, the systems-level mode of action of plant viruses remains poorly understood. Here, we followed a high-throughput yeast two-hybrid screening to identify 378 novel virus-host protein-protein interactions between Turnip mosaic virus (TuMV), a representative plant RNA virus, and Arabidopsis thaliana, one of its natural hosts. We found the RNA-dependent RNA polymerase NIb as the virus protein with the largest number of contacts. We verified a subset of 25 selected interactions in planta by bimolecular fluorescence complementation assays. We then constructed a comprehensive network comprising 399 TuMV-A. thaliana interactions to perform, together with intravirus and intrahost connections, detailed computational analyses. In particular, we found that the host proteins targeted by the virus participate in a higher number of infection-related functions, are more connected and have an increased capacity to spread information throughout the cell proteome, display higher expression levels, and have been subject to stronger purifying selection than expected by chance. Overall, our results provide a comprehensive mechanistic description of a plant virus-host interplay, with potential impact on disease etiology, and reveal that plant and animal viruses share fundamental features in their mode of action.