To our knowledge, this study is the first to demonstrate how naturally occurring, genetically determined differences in the interactions between a virus and its host can tilt the balance between the various functions of IFN-a/b towards conditions promoting the induction of early adaptive immunity rather than towards the development of a state of transient immunosuppression. Our data also confirm that NK cell antiviral functions prevent the generation of a chronic state of CD8 T cell activation later during the infection that may otherwise lead to immunopathology. A key question for future studies will be to determine how general this function of NK cells is for antiviral defense. Such mechanisms may also be in place during HIV infection where genetic [55] or functional [56] [57] [58] evidences suggest a role in the variation of NK cell functions for resistance or susceptibility to the development of AIDS, where detrimental effects of excessive levels of IFN-a/b [59] or of pro-inflammatory cytokines [60, 61] have been recently suggested, and where the initiation of antiviral CD8 T cell responses appears delayed [62] [63] [64] . This could also be the case for infections with highly pathogenic strains of influenza, as excessive production of pro-inflammatory cytokines have been shown to occur and proposed to play a crucial role in immunopathology [65, 66] , while NK cells can confer resistance through recognition of infected cells by the NKp46 receptor [67] . Very recently, researchers have demonstrated that human NK cells are able to recognize DCs infected with the influenza or Ebola viruses [68, 69] , while a correlation between unregulated IFN-a/b responses and a malfunction of the switch from innate to adaptive immunity has been reported during fatal SARS [70] , which further highlight the potential relevance of our observations to a variety of viral infections. Thus, it will be important to determine the impact of NK cell function on the modulation of innate and adaptive immunity and on the development of immunopathology in other models of viral infection. Moreover, our results imply that in individuals susceptible to such viral infections, pharmacological control of viral replication very early should benefit them not only by directly limiting viral cytopathogenicity, but also by establishing conditions better suited to the development of balanced, protective immunity, since this is the case in mice susceptible to MCMV infection when viral replication is controlled by drug treatment.