Despite the existence of these viral PKR-evading strategies, the importance of PKR for type-I IFN production has been strongly debated over the years and even considered dispensable since the discovery of the innate immunity function of the DExD/H box RNA helicases [27, 28] . However, several PKR-deficient cell types have reduced type-I IFN production in response to poly I:C [23, 29, 30] , while PKR was demonstrated to be required for IFNa/b production in response to a subset of RNA viruses including Theiler's murine encephalomyelitis, West Nile (WNV) and Semliki Forest virus (SFV), but not influenza, Newcastle disease, nor Sendai virus [31, 32, 33, 34] . These studies raise therefore the possibility that some but not all viruses induce IFN-a/b in a PKRdependent and cell specific manner. Infection of PKR or RNAse L deficient mice demonstrated that these enzymes were not absolutely necessary for type I IFN-mediated protection from alphaviruses such as SFV or WNV, but still contributed to levels of serum IFN and clearance of infectious virus from the central nervous system [25, 35] . Similarly, deficient mice for both PKR and RNAse L showed no increase in morbidity following SINV infection, although, like during WNV infection, increased viral loads in draining lymph nodes were observed [35, 36] . These observations support a non-redundant and cell specific role for these enzymes in the amplification of type-I IFN responses to viral infection more than in their initiation [31, 32, 35] . Nevertheless, the exacerbated phenotypes observed upon alphavirus infection of mice deficient for type-I IFN receptor (IFNAR), underlines the limits of the individual contributions of PKR and RNAse L to the anti-viral resistance of adult animals [10, 35, 36] .