GADD34 expression is therefore necessary to allow normal type-I interferon production during viral infection and to promote the survival of young infected animals. We could circumvent the age-related acquisition of viral resistance in GADD34 DC/DC mice to 17 days, since mice inoculated at that age survived CHIKV inoculation. In these animals, 3 days post-infection, enhanced viral replication was observed in the spleen and muscles, matching the relatively low level of type-IFN production in these tissues ( Figure 7C ). Functional GADD34 is therefore required to mount a normal innate response against the virus, but in older mice type-I IFN production by non-infected innate cells is probably capable to gradually overcome GADD34-deficiency and limit viral proliferation in vital organs, such as the heart.