Making sense of how pathogens respond to the complex web of interacting receptors and signaling pathways is a major challenge. In Cell, Hacohen and colleagues use an integrated approach of transcriptomics, proteomics and perturbation to unpick the complexity of the antiviral response. By examining dendritic cells stimulated by Toll-like receptor agonists or live virus, they confirm the importance of many classic molecules and pathways involved in antiviral responses. However, they also show that the polo-like kinases (PLKs) PLK2 and PLK4 have mutually redundant, but together critical, activatory roles in the antiviral response. They use a small-molecule PLK inhibitor to confirm the importance of PLKs in antiviral immunity both in vitro and in vivo. So far, PLKs have been examined only in the context of the cell cycle, so their involvement in the antiviral response is wholly unexpected, and this demonstrates the utility of such an unbiased approach.
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Fehervari, Z. Mining antiviral complexity. Nat Immunol 13, 19 (2012). https://doi.org/10.1038/ni.2197
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DOI: https://doi.org/10.1038/ni.2197