Nucleic acids detection by multiple molecular sensors results in type-I interferon production, which protects cells and tissues from viral infections. At the intracellular level, the detection of double-stranded RNA by one of these sensors, the dsRNA-dependent protein kinase also leads to the profound inhibition of protein synthesis. We describe here that the inducible phosphatase 1 co-factor Ppp1r15a/ GADD34, a well known player in the endoplasmic reticulum unfolded protein response (UPR), is activated during double-stranded RNA detection and is absolutely necessary to allow cytokine production in cells exposed to poly I:C or Chikungunya virus. Our data shows that the cellular response to nucleic acids can reveal unanticipated connections between innate immunity and fundamental stress pathways, such as the ATF4 branch of the UPR. When levels of IFN-ß were quantified in culture supernatants and compared to total protein synthesis intensity, we found that most of the cytokine production occurred after 4 to 8 h of pIC delivery (Fig. 1E , WT, and S1D), a time at which mRNA translation was already considerably decreased ( Fig. 1A and S1E). We measured the amount of cytokine produced in NIH-3T3 cells at a time (7 h) at which translation was already strongly inhibited ( Fig. 1G and 1F ). To prove that IFN-b production truly occurred during this poly I:C-induced translation arrest, cells exposed for 7 h to poly I:C were washed and old culture supernatants replaced with fresh media for 1 h (with or without CHX), prior translation monitoring (Fig. 1F , right) and IFN-ß dosage (Fig. 1G , right). We observed that close to 30% of the total IFN-ß produced over 8 h of poly I:C stimulation is achieved during this 1 h period, despite a close to undetectable protein synthesis in the dsRNA-treated cells (Fig. 1F ). The neo synthetic nature of this IFN was further demonstrated by the absence of the cytokine in CHX-treated cell supernatants. IFN-b production in response to poly I:C is therefore likely to be specifically regulated and occurs to a large extent independently of the globally repressed translational context. As previously observed in MEFs, IFN-ß production in response to poly I:C was independent of PKR ( Fig. 1E ) [31] . This suggests that although its production occurs during cap-mediated translation inhibition, it does not directly depend on a specialized open reading frame organization, as described for the translation of the mRNAs coding for the UPR transcription factor ATF4 or the SV 26S mRNA upon eIF2a phosphorylation [26, 49] . This hypothesis is also supported by the ability of MEFs expressing the non-phosphorylatable eIF2a Ser 51 to Ala mutant (eIF2a A/A), to produce normal levels of IFN-ß in response to poly I:C (Fig. 1E) , while global translation was not inhibited by poly I:C in these cells (Fig. S2 ).