Using global approaches and high-throughput technologies in virology brings a new vision of the infections physiology and allows the identification of cellular factors, mandatory for viral life cycle, that could be targeted by original therapeutic agents. It opens perspectives for the treatment of viral infections by acting on cellular pathways that the virus must use for its own replication. Combining these new molecules with classical antiviral drugs and immunomodulators diversifies and enlarges the antiviral arsenal and contributes to fight drug resistance.Our laboratory and others are constructing virus-human interactomes to propose a comprehensive analysis of viral infection at the cellular level. Studying these infection maps, where the viral infection can be visualized as perturbation of the human protein-protein interaction network, and identifying the biological functions that are impaired by these perturbations may lead to discovery of new therapeutic targets. These virus-human interaction maps are constructed in a stringent yeast two-hybrid system by screening human cDNA libraries with viral proteins as bait and integrating interactions mined from literature and public databases.
Key words:Yeast two-hybrid screen, Mating, Yeast two-hybrid array, Protein-protein interactionThe rapidly growing knowledge of protein-protein interaction networks (interactomes) for model organisms and human provides a network-based model to understand molecular and cellular biology. Recently, virus-host relationships also began to be studied at the proteome level by identifying interactions between viral and host-cell proteins (1-5), as reviewed in ref. 6. These virus-host interactomes compose a repertoire of interactions between viral and human proteins that can be analyzed in a network approach. By this mean, viral infections can be viewed as the expression of new constraints imposed by the virus on the cellular interactome.