Systems Virology: Why everybody wants to measure everything

Virologists have long known that viral pathogenesis must be studied from the standpoint of both the virus and the host. Nevertheless, given its relative simplicity, studying the virus has always been more tractable. As outlined in the previous chapters, virus-centric approaches have yielded a tremendous amount of information about viral genetics, viral replication cycles, and host and tissue tropisms. Along the way have come insights into host innate and adaptive immune responses and the many ways in which viruses antagonize these responses while exploiting other cellular processes to their advantage. The sequencing of the human genome, however, dramatically changed the field of viral pathogenesis. Virologists are now able to move beyond virus-centric or single-gene approaches and instead investigate the host response to infection on a genome-wide scale. In this chapter, we focus on the insights into viral pathogenesis that are provided by examining the host transcriptional response, including the dynamics of innate and acquired immunity, diagnostic signatures, and the identification of targets for antiviral drugs.