PSEUDORABIES VIRUS-INDUCED LEUKOCYTE TRAFFICKING INTO THE RAT CENTRAL-NERVOUS-SYSTEM

When the swine alphaherpesvirus pseudorabies virus (PRV) infects the r at retina, it replicates in retinal ganglion cells and invades the cen tral nervous system (CNS) via anterograde transynaptic spread through axons in the optic nerve, Virus can also spread to the CNS via retrogr ade transport through the oculomotor nucleus that innervates extraocul ar muscles of the eye, Since retrograde infection of the CNS precedes anterograde transynaptic infection, the temporal sequence of infection of the CNS depends on the route of invasion. Thus, motor neurons are infected first (retrograde infection), followed by CNS neurons innerva ted by the optic nerve (anterograde transynaptic infection). This temp oral separation in the appearance of virus in separate groups of neuro ns enabled us to compare the immune responses to different stages of C NS infection in the same animal. The data revealed focal trafficking o f peripheral immune cells into areas of the CNS infected by retrograde or anterograde transport after PRV Becker was injected into the vitre ous body of the eye, Cells expressing the leukocyte common antigen, CD 45(+), entered the area of infection from local capillaries prior to a ny overt expression of neuropathology, and quantitative analysis demon strated that the number of cells increased in proportion to the number of infected neurons within a given region, Recruitment of cells of mo nocyte/macrophage lineage began prior to the appearance of CD8(+) cyto toxic lymphocytes, which were, in turn, followed by CD4(+) lymphocytes . These data demonstrate that PRV replication in CNS neurons stimulate s the focal infiltration of specific classes of CD45(+) cells in a tim e-dependent, temporally organized fashion that is correlated directly with the number of infected neurons and the time that a given region h as been infected.