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.

Dissemination of wild-type and gC-, gE- and gI-deleted mutants of Aujeszky's disease virus in the maxillary nerve and trigeminal ganglion of pigs after intranasal inoculation

“…After uptake and primary replication in the upper respiratory tract, ADV spreads towards the central nervous system (CNS) by means of one or more of the cranial nerves such as the olfactory and trigeminal nerves (McFerran & Dow, 1965;Sabo et al, 1969;Wittmann et al, 1980). It is generally accepted that the neuron plays an important role in neural invasion by herpesviruses such as ADV and herpes simplex virus type 1 (HSV-1) (Cook & Stevens, 1973;Field & Hill, 1974;Hill et al, 1972;Kristensson et al, 1971 ;McCracken et al, 1973;Wildy, 1967). The replication cycle of herpesviruses in neurons has been studied most frequently with HSV-1 in rat or human neuronal cell cultures (Lycke et al, 1984(Lycke et al, , 1988.…”

“…Information regarding in vivo transport of herpesviruses has been derived by studying the kinetics of dissemination of infectious HSV-1 in spinal nerves and their corresponding spinal ganglia (Cook & Stevens, 1973;Hill et al, 1972;Klein & DeStefano, 1983;Kristensson et al, 1971;Wildy, 1967). The ganglion contains the neural cell bodies and the nerves their extensions.…”

Vaccine-Induced Serum Immunoglobin Contributes to Protection from Herpes Simplex Virus Type 2 Genital Infection in the Presence of Immune T Cells

“…Most controversial is the role of HSV-specific serum IgG in protection of the nervous system. Studies using corneal and footpad routes of challenge with HSV have indicated no decrease in latent infection in mice receiving immune serum (41,61). Using the genital route of challenge, Schneweis et al demonstrated a decrease in the number of acutely and latently infected DRG upon transfer of immune serum to naive recipients (51), an observation that was recently confirmed in HSV-immune, B-cell-deficient mice…”

Molecular Aspects of Herpes Simplex Virus I Latency, Reactivation, and Recurrence

“…During the initial infection, HSV-I multiplies in the epithelium, invades local nerve endings, and travels by retrograde axonal transport (Johnson, 1964;Wildy, 1967) to neuronal cell bodies in regional sensory ganglia (Stevens and Cook, 1971;Hill et al, 1972). Although some sensory neurons permit productive infection to occur and are destroyed, most sensory neurons survive the infection and retain the virus in a latent state.…”