as controls to induce GADD34. Immunoblot of tubulin is shown as equal loading control. C) Amount of IFN-b (left panel) and IL-6 (right panel) in cell culture supernatants of WT and GADD34 DC/DC MEFs after 6 h of poly I:C stimulation. Mock are samples treated with lipofectamine alone. Data are mean 6 standard deviation of five (IFN-b) and three (IL-6) independent experiments. D) Transcription of IFN-b, IL-6, PKR and Cystatin C was analyzed by qPCR in samples of WT and GADD34 DC/DC MEFs treated with poly I:C (pI:C). Mock represent samples treated with lipofectamine alone. E) WT and GADD34 DC/DC MEFs were transfected overnight with an expression plasmid carrying the murine GADD34 (G34) cDNA and then treated with poly I:C for 6 h. IFN-b production was quantified by ELISA, left panel, in cell culture supernatants and plotted as a ratio of IFN-b to total cell proteins to compensate for different cell mortality levels induced by the transfection. In the right panel immunoblots for GADD34 and P-eIF2a in the same experimental conditions are shown. One representative analysis of 3 independent experiments is shown. doi:10.1371/journal.ppat.1002708.g004 GADD34 is necessary for IFN production and to control Chikungunya virus infection Fibroblasts of both human and mouse origin constitute a major target cell of Chikungunya virus (CHIKV) during the acute phase of infection [59] . In adult mice with a totally abrogated type-I IFN signaling, CHIKV-associated disease is particularly severe and correlates with higher viral loads. Importantly, mice with one copy of the IFN-a/ß receptor (IFNAR) gene develop a mild disease, strengthening the implication of type-I IFN signaling in the control of CHIKV replication [59] . Recently, human fibroblasts infection by CHIKV was shown to induce IFN-a/ß mRNA transcription, while preventing mRNA translation and secretion of these antiviral cytokines. CHIKV was found to trigger eIF2a phosphorylation through PKR activation, however this response is not required for the block of host protein synthesis [15] .