Signaling events that occur early following viral infection are often critical in dictating outcome. Recent studies have highlighted the importance of innate immune cells in contributing to a ). Monocytes are also attracted into the CNS via the chemokine CCL5 and its receptor CCR5. Neutrophils and monocytes participate in the degradation of the bloodbrain barrier (BBB), in part through the release of the matrix metalloproteinase MMP-9, and therefore ensure successive infiltration of virus-specific lymphocytes into the CNS. (B) During the acute stage of disease, astrocytes, microglia, neurons, and endothelial cells continue to secrete chemokines, serving to attract activated T lymphocytes, NK cells, and monocytes into the CNS. CD8+ and CD4+ T lymphocytes bearing the receptor CXCR3 and/or protective response, and we are just now learning how chemokines are involved in attracting these cells to the CNS. Infection of mice with neurotropic virus such as HSV-1 and JHMV results in the rapid accumulation of neutrophils to the CNS [13, 14] . Studies using the JHMV model system have provided insight into the functional relevance of neutrophil migration to the CNS, as these cells are required to contribute to the permeabilization of the BBB [14] . During JHMV infection, astrocyte-and endothelial-derived expression of ELR+ (glutamic acid-leucine-arginine) CXC chemokines, including CXCL1, attracts CXCR2-reactive neutrophils to the CNS [14] . Neutralization of this signaling axis specifically abrogates neutrophil infiltration, thereby preventing BBB degradation and the ensuing entry of protective JHMV-specific T lymphocytes [14] . In the absence of CXCR2 signaling, JHMVinfected mice experience higher viral loads and quickly succumb to infection, indicating that neutrophil targeting of the CNS is critical in host defense [14] . Conversely, McGavern and colleagues have suggested that during acute LCMV infection (Armstrong strain), cytotoxic T lymphocyte (CTL)-mediated chemokine gene expression contributes to fatal meningoencephalitis, in part, by attracting neutrophils and monocytes into the CNS, and this is associated with fatal vascular permeability and seizures, thus highlighting a detrimental role for neutrophils in response to viral infection [15] . In addition to enhancing the permeabilization of the BBB by recruiting neutrophils and monocytes, chemokines can also function as gatekeepers regulating leukocyte penetration into the parenchyma. Following WNV infection of the CNS, CXCL12 retains antigen-sensitized lymphocytes within the perivascular space. Antagonism of CXCR4, the receptor for CXCL12, enhances T lymphocyte entry into the CNS parenchyma, and this correlates with reduced WNV burden, enhanced survival, and limited neuropathology [16] . Thus, expression of chemokines early in response to infection with neurotropic viruses aids in effective host defense by promoting vascular permeability and regulating parenchymal lymphocyte infiltration ( Figure 1A ). However, it should be emphasized that the consequences of BBB degradation can vary from efficient viral clearance to fatal encephalitis and seizures, depending upon the virus and the route of infection.