1970s after the different western Indian Ocean islands and Indian subcontinent disease outbreaks [68, 69] . These particular symptoms and complications might therefore be the consequences of great variation in the tissue-specific type-I IFN levels induced in CHIKV-infected patients, who might display particular polymorphisms in their innate viral sensing pathways increasing their peculiar susceptibility to viral dissemination in the heart. Importantly, our data reveal a link between pathogen-associated molecular patterns (PAMPs) and the UPR through the activation of the eIF2-a/ATF4 branch [70] . Similarly, several laboratories have reported that TLR stimulation activates the XBP-1 branch of the UPR and that XBP-1 production was needed to promote a sustained production of inflammatory mediators, including IL-6 [71, 72] . Here, we identify GADD34 as a novel functional link between ISR and PAMPs detection in MEFs, required for the production of cytokines including type-I IFN. It will now be important to explore the therapeutic potential of targeting GADD34 to reduce cytokines overproduction during inflammatory conditions. 