Supporting the importance of Cul4b in CD8+ T cell anti-viral activity, mice lacking Cul4b in T cells were unable to clear virus (LCMV or Ectromelia), and after adoptive transfer, Cul4b-deficient LCMV-specific CD8+ T cells were unable to expand into memory or effector cells following virus infection. Here, CUL4B is linked to viral infectious disease.