As in Humans, CHIKV pathogenicity is strongly agedependent in mice, and in less than 12 day-old mouse neonates, CHIKV induces a severe disease accompanied with a high mortality rate [59] . GADD34 function was therefore evaluated in this more sensitive context by injecting intradermally CHIKV to FVB (WT) and GADD34 DC/DC neonatal mice. As previously observed for C57/BL6 mice [59] , when CHIKV was inoculated to FVB neonates, a rate of 50% of mortality was observed 3 days after the infection of 9-day-old mice, while 12-day-old pups were found essentially resistant to the virus lethal effect (Fig. 7A ). Strongly contrasting with these results, all CHIKV infected GADD34 DC/DC neonates died within 3-5 days post inoculation whatever their age (Fig. 7A ). When infection was monitored 5 days post-inoculation of 12-day-old mice at, GADD34 DC/DC pups displayed considerably more elevated CHIKV titers (10-100 folds) in most organs tested, including liver, muscle, spleen and joints, the later being primarily targeted by the virus (Fig. 7B, left) . As expected, and in full agreement with the in vitro data, infected GADD34 DC/DC tissues showed a considerably reduced IFN-ß production (40-50%) compared to control tissues ( Figure 7B, right) , while serum levels were reduced by 20% (not shown). Although Infectious virus was poorly detected in the heart of WT animals, elevated titers of virus were observed in the heart of GADD34-deficient pups, matching the limited production of IFN in this organ. We further investigated the possible pathological consequences of cardiac tissue infection by carrying-out comparative histopathology. Hearts of infected GADD34-deficient animals displayed severe cardiomyocytes necrosis with inflammatory infiltrates by monocytes/ macrophages and very important calcium deposition (Fig. 8) , all being indicative signs of grave necrotic myocarditis. As a consequence, the left ventricles were strongly dilated, being probably the cause of acute cardiac failures and of the important death rate observed in GADD34 DC/DC infected pups. Histology of infected FVB mice hearts was, however, normal with only few inflammatory cells (mainly lymphocytes) observed in the close vicinity of capillaries.