Finally, we asked whether interruption of NKG2D-mediated recognition of NKG2D ligands was sufficient to alter viral load within the hippocampus. We used the CX5 function blocking antibody following a therapeutic regime adapted from Lanier and colleagues (100 ug/mouse i.p. on −1, +1, and +4 dpi; kindly provided by Dr. Lanier, UCSF) . Control mice received an equivalent dose of polyclonal rat IgG . Plaque assay (Pavelko et al, 1998) of freshly excised brain homogenates at 7 dpi revealed that CX5 treatment led to 9 ± 2 times more infectious virus as compared to control IgGtreated mice (U(5,5)=15, P=0.008, Mann-Whitney rank sum test; mean ± 95% CI) ( Figure  3C ). Based on these observations, we propose that VP2-specific CTLs expressing NKG2D recognize NKG2D ligands such as Rae1 and H60 expressed on infected cells within the brain and thereby engage an enhanced cytotoxic response (Markiewicz et al, 2005 ) that contributes to the clearance of picornaviruses from the CNS.