However, our results indicate that in our system, transmigration of monocytes and T cells in the presence of CCL2 did not further alter the permeability of the infected BBB model. However, this does not rule the possibility of other chemokines such as the CCL5 in chemoattracting leukocytes to the lower chamber of the model. Further, our data clearly demonstrate that the negligible leukocyte adhesion to uninfected HBMVE did not appear to be dependent upon the interaction with CAMs since blocking antibodies did not further decrease adhesion in the mock-infected controls. On the other hand, increased leukocyte adhesion to the infected HBMVE can be attributed to the increased expression of CAM’s based on the observation that blocking antibodies markedly reduced the number of monocytes and lymphocytes adhered to the HBMVE. Our results are similar to other studies using Theiler’s murine encephalitis virus demonstrating reversal in the leukocyte adhesion and transmigration in the presence of VCAM-1 in infected endothelial cells. The infiltration of the leukocytes can have multiple downstream effects in WNV pathogenesis. First, WNV might promote its entry into the CNS through the BBB in a ‘Trojan horse’ manner, where infected monocytes and T cells gain entry into the CNS and disseminate virus to the neighboring brain cells. Such phenomenon has already been proposed and demonstrated in infection with several neurotropic pathogens including HIV, Venezuelan equine encephalitis virus and T.gondii. Second, recruited immune cells might contribute to immunopathology. Though leukocyte infiltration is critical to clear WNV from the brain, they may also be one of the causes of massive inflammation in the CNS leading to neuronal death via apoptosis. WNV-infected and activated monocytes and T cells have been shown to produce inflammatory cytokines and chemotactic chemokines. Recently, production of nitric oxide by WNV-infected macrophages in the brain has been associated with the pathogenic function of leukocytes. Lastly, uncontrolled leukocyte transmigration can be one of the causes of the WNV-associated BBB disruption observed in vivo. Our current findings strongly suggest important role of specific WNVinduced CAMs in modulating the extent of transmigration of peripheral leukocytes into the brain, thereby causing BBB disruption. In this study, we used a cocktail of blocking antibodies against all three CAM’s, VCAM-1, ICAM and E-selectin instead of blocking each of these CAM’s individually to address their independent roles and relative contribution in BBB disruption. We considered this approach based on the fact that all of these WNV-induced CAM’s are critical in leukocyte trafficking and blocking one of them would not significantly affect different events underlying leukocyte transmigration. Consistent with this fact, it is shown that combinational treatment with anti-MAdCAM-1, VCAM-1 and ICAM-1 monoclonal antibodies led to more rapid remission in the SAR131675 experimental autoimmune encephalitis model of MS than that obtained with individual antibodies alone.