ICAM-1 and VCAM-1 have redundant roles in mediating shear resistant arrest of encephalitogenic T cells to the BBB endothelial cells and only in the functional absence of both was the complete abrogation of T cell arrest on the BBB observed. Increasing evidence suggests that the ability of the WNV to invade CNS is strain specific. The non-neurovirulent nature of Eg101 is attributed to several factors including differences in innate immune response and not able to cross the BBB, however its interaction with BBB cells is not yet characterized. Human brain endothelial cell infection with Eg101 is not reported so far and our data for the first time indicate that the replication kinetics of Eg101 and Ny99 strain in HBMVE cells was comparable. This observation is indirectly supported by similar studies demonstrating that another non-pathogenic WNV strain, MAD78 can replicate as efficiently as NY strain in BBBendothelial cells. On the other hand, Hasebe and group demonstrated that virus like particles of NY99 transported efficiently from the apical to basolateral side of human endothelial cells, whereas Eg101-VLPs hardly transported. Further in vivo studies are warranted to delineate differences between NY99 and Eg101 at the level of CNS entry, BBB disruption and leukocyte infiltration. However, our results imply that the difference in the neuroinvasive ability between Eg101 and NY99 is not at the level of virus replication and subsequent induction of CAMs in HBMVE cells. It is likely that Eg101 is less neuroinvasive EX 527 HDAC inhibitor because the host immune response is able to clear Eg101 more efficiently in the periphery as compared to NY99, which may lead to lower viremia resulting in reduced CNS entry of Eg101. Targeting CAMs either directly using neutralizing antibodies or by blocking upstream signaling in animal models is being proposed as an attractive and feasible strategy for therapeutic intervention of reducing transendothelial migration of leukocytes and neuroinflammation in inflammatory diseases such as asthma and polymicrobial sepsis. Giri et al. showed that b-amyloidmediated migration of monocytes across BBB model was inhibited by blocking CAMs. The data is limited in virus infections, although it has been shown that Anandamide inhibits Theiler’s virus induced VCAM-1 in brain endothelial cells resulting in reduced leukocyte transmigration across the BBB model. Further, its has been recently demonstrated that treatment with VLA-4 antibody can reduce CNS infiltration of macrophages and increase survival of mice infected with the Sarafend strain of WNV via intranasal route following. These studies collectively suggest the possibility of therapeutic effects of temporarily targeting specific CAMs to improve pathogenesis of WNV and other encephalitis causing viruses. In summary, our results provide insights into the mechanisms by which WNV modulates brain endothelium to facilitate leukocyte trafficking into the CNS. Increased expression of specific CAMs may be a pathological event associated with WNV infection and may contribute to BBB disruption in vivo.