Acute infection with influenza, HBV, dengue, and adenovirus induce activation (CD38+ HLA-DR+) of HCMV- and EBV-specific CD8 T cells. In one influenza patient, 1/4 of activated CD8 T cells at onset were HCMV-specific, and influenza-specific CD8 T cells could not be detected until day 5. In addition, IL-15 preferentially activates memory CD8 T cells specific for chronic infections, augments anti-viral cytokine production with TCR stimulation, and is sufficient for spontaneous IFN-γ production. Here, CD8A is linked to influenza.