The Pathogenesis of Pseudorabies in Mice following Peripheral Inoculation

Researchers inoculated three-week-old mice with pseudorabies virus through the hind foot pad and tracked virus spread through various tissues. The virus followed a characteristic progression: first appearing in the foot pad at 18 hours, then sequentially in the sciatic nerve, dorsal root ganglion, spinal cord (lower to upper), and brain by 60 hours post-inoculation. The virus rarely appeared in the liver and never in the spleen or heart under normal conditions. Electron microscopy revealed that neurons, not glial cells, were primarily responsible for facilitating virus spread within the nervous system. When the sciatic and femoral nerves were surgically sectioned or ligated before viral inoculation, mice showed reduced mortality and delayed disease onset, confirming neural spread as the primary transmission route. Immunosympathectomy (destruction of sympathetic nerve fibers) reduced virus recovery from adrenal glands and kidneys, suggesting the autonomic nervous system plays a role in pathogenesis.

Key findings

• Pseudorabies virus spreads centripetally from peripheral inoculation site through peripheral nerves to the central nervous system in a characteristic temporal sequence
• Neurons rather than glial cells are the primary facilitators of virus spread within the nervous system, as demonstrated by electron microscopy showing intact replication in neurons but abortive infection in glia
• Surgical section or ligation of sciatic and femoral nerves significantly reduces mortality and delays disease onset, demonstrating that neural pathways are essential for normal viral spread
• The autonomic nervous system is involved in viral pathogenesis, as immunosympathectomy reduces virus recovery from adrenal glands and kidneys
• Virus spreads at approximately 42 mm/day along the sciatic nerve, consistent with axoplasmic transport mechanisms