Viral infections have a tremendous impact on human health, yet little is known about the interactions between the pathogen and its host. We, therefore, propose a Systems Biology Approach to analyze virus infections in different biological systems, identify pathogen-host interactions, characterize host cell responses, and correlate these data with bioinformatics approaches. Influenza viruses are an ideal model system due to their impact on human health and the global economy. A ‘Virology/Cell Biology Unit’ will characterize influenza viral replication and pathogenicity in cells and animals and identify host-virus interaction partners. A ‘Host Cell Response Unit’ will study the cellular transcriptome in response to viral infection. Data analysis and modeling of cellular responses will be conducted by the ‘Computational Systems Biology Unit’. These studies will lead to a comprehensive understanding of the cellular networks activated upon viral infections and are, therefore, expected to establish new concepts in study of viral diseases.