The progression of herpes simplex virus to the central nervous system of the mouse

Abstract

1. The strain HFEM of herpes simplex virus is highly virulent for the 5-week-old mouse when inoculated intracerebrally; the LD50 and the ID50 both being close to the egg infectious unit. It is also virulent when given intraspinally.2. When inoculated peripherally it seldom causes nervous symptoms in the normal mouse but regularly does so if inoculated into skin which has previously been given a subcutaneous injection of 10% sodium chloride.3. After intradermal inoculation of pretreated mice with strain HFEM, the paralysis is preceded by the appearance of infective virus in the blood, the sciatic nerve and the central nervous system. Invasion of the central nervous system is prevented by interruption of the local peripheral nerve.4. There is no evidence that virus enters the central nervous system by way of the lymphatics or by direct extension through the tissues.5. After intravenous inoculation virus does not invade the central nervous system unless (a) massive inocula are used or (b) the brain is traumatized by injecting sterile saline. After peripheral inoculation insufficient virus to infect even traumatized brain seems to circulate in the cerebral vessels. Paralysis and invasion of the central nervous system are not prevented by circulating neutralizing antibody given 18 hours after inoculation.It therefore appears that invasion of the central nervous system takes place only by way of the peripheral nerve.