Systems virology: host-directed approaches to viral pathogenesis and drug targeting

Key Points Systems biology approaches are required to advance our understanding of virus–host interactions, how these interactions cause disease and, ultimately, how to improve diagnostics, therapeutics and vaccines. Over the past decade, the field of systems virology has evolved from using first-generation microarrays to the integration of multidimensional data sets. This has resulted in significant findings, including the identification of gene expression signatures that are predictive of viral pathogenesis and vaccine efficacy, insights into how viruses disrupt cellular metabolism, and the mapping of virus–host interactomes. To fulfil its initial promise of revolutionizing our understanding of virus–host interactions, the field of systems virology must move beyond just the listing of molecules that are differentially expressed following viral infection; it must now look to define the relationships between key host molecules and their interactions with viral components. Several key computational challenges must be addressed in order to move into this new phase of systems virology, including consideration of nonlinear relationships such as the dynamics of the system, the integration of multidimensional data sets and the identification of causal relationships. Virologists, computer scientists and mathematicians must combine their skills and expertise in applying systems approaches to untangle the complex question of how viruses kill.