DIFFERENT PATTERNS OF NEURONAL INFECTION AFTER INTRACEREBRAL INJECTION OF 2 STRAINS OF PSEUDORABIES VIRUS

Pseudorabies virus (PRV), a swine neurotropic alphaherpesvirus, is kno wn to invade the central nervous system (CNS) of a variety of animal s pecies through peripherally projecting axons, replicate in the parent neurons, and then pass transsynaptically to infect other neurons of a circuit. Studies of the human pathogen herpes simplex virus type 1 hav e reported differences in the direction of transport of two strains of this virus after direct injection into the primate motor cortex. In t he present study we examined the direction of transport of virulent an d attenuated strains of PRV, utilizing injections into the rat prefron tal cortex to evaluate specific movement of virus through CNS circuitr y, The data demonstrate strain-dependent patterns of infection consist ent with bidirectional (anterograde and retrograde) transport of virul ent virus and unidirectional (retrograde) transport of attenuated PRV from the site of injection. The distribution of infected neurons and t he extent of transsynaptic passage also suggest that a release defect in the attenuated strain reduces the apparent rate of viral transport through neuronal circuitry, Finally, injection of different concentrat ions of virus influenced the onset of replication within a neural circ uit. Taken together, these data suggest that viral envelope glycoprote ins and virus concentration at the site of injection are important det erminants of the rate and direction of viral transport through a multi synaptic circuit in the CNS.