Gene expression patterns supply insight into complex biological networks that provide the organization in which viruses and host cells interact. Measles virus (MV) is an important human pathogen that induces transient immunosuppression followed by life-long immunity in infected individuals. Dendritic cells (DCs) are potent antigen-presenting cells that initiate the immune response to pathogens and are postulated to play a role in MV-induced immunosuppression. To better understand the interaction of MV with DCs, we examined the gene expression changes that occur over the first 24 h after infection and compared these changes to those induced by other viral, bacterial, and fungal pathogens. There were 1,553 significantly regulated genes with nearly 60% of them down-regulated. MV-infected DCs up-regulated a core of genes associated with maturation of antigen-presenting function and migration to lymph nodes but also included genes for IFN-regulatory factors 1 and 7, 2'5' oligoadenylate synthetase, Mx, and TNF superfamily proteins 2, 7, 9, and 10 (TNF-related apoptosis-inducing ligand). MV induced genes for IFNs, ILs, chemokines, antiviral proteins, histones, and metallothioneins, many of which were also induced by influenza virus, whereas genes for protein synthesis and oxidative phosphorylation were down-regulated. Unique to MV were the induction of genes for a broad array of IFN-alphas and the failure to up-regulate dsRNA-dependent protein kinase. These results provide a modular view of common and unique DC responses after infection and suggest mechanisms by which MV may modulate the immune response.