FIGURE 2.

The role of CCR5 during flavivirus-induced encephalitis. During WNV and Japanese encephalitis virus (JEV) infection in mice, the migration of CD4⁺ T-cells, CD8⁺ T-cells, NK-cells and monocytes from the blood into CNS is required for efficient control of viral replication and recovery (upper). In the absence of CCR5 in mice, the migration of these leukocytes into the CNS is delayed and/or severely impaired (lower). During JEV infection, the absence of CCR5 also results in inefficient NK and CD8⁺ T-cell effector functions as well. Although the function of CCR5 has not been evaluated during WNV infection in humans, homozygosity for the complete loss-of-function mutation, CCR5Δ32, has been correlated with increased severity of WNV and tick borne encephalitis virus infections. It is anticipated that blockade of CCR5, either in mice or humans, may increase susceptibility to neurotropic flaviviruses.