scholarly journals LATENT HERPES SIMPLEX VIRUS IN THE CENTRAL NERVOUS SYSTEM OF RABBITS AND MICE

1973 ◽  
Vol 138 (3) ◽  
pp. 740-744 ◽  
Author(s):  
F. B. Knotts ◽  
M. L. Cook ◽  
J. G. Stevens
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Herpes Simplex Virus ◽  
Herpes Simplex ◽  
Organ Cultures ◽  
The Central Nervous System ◽  
Simplex Virus ◽  
The Brain

Herpes simplex virus (HSV) type 1 induces a long-standing latent infection in the central nervous system of mice and rabbits. The infection was extablished in the brain stems of rabbits after corneal inoculation of the virus, and in the spinal cords of mice after rear footpad infection. In these animals, infectious virus could not be recovered by direct isolation from tissues; it was detected only after the tissues were maintained as organ cultures in vitro.

scholarly journals Spread and Replication of and Immune Response to γ134.5-Negative Herpes Simplex Virus Type 1 Vectors in BALB/c Mice

2004 ◽  
Vol 78 (23) ◽  
pp. 13139-13152 ◽  
Author(s):  
Eeva K. Broberg ◽  
Jutta Peltoniemi ◽  
Michaela Nygårdas ◽  
Tero Vahlberg ◽  
Matias Röyttä ◽  
...  
Keyword(s):  
Central Nervous System ◽  
Immune Response ◽  
Nervous System ◽  
Herpes Simplex ◽  
Trigeminal Ganglia ◽  
Rt Pcr ◽  
The Central Nervous System ◽  
Simplex Virus ◽  
The Brain

ABSTRACT We have previously shown that intracranial infection of herpes simplex virus type 1 (HSV-1) vector R8306 expressing interleukin-4 (IL-4) can abolish symptoms of experimental autoimmune encephalomyelitis, which is used as a model for human multiple sclerosis (Broberg et al., Gene Ther. 8:769-777, 2001). The aim of the current study was to search for means other than intracranial injection to deliver HSV-derived vectors to the central nervous system of mice. We also aimed to study the replication efficiency of these vectors in nervous system tissues and to elucidate the effects of the viruses on the immune response. We studied the spread and replication of the following viruses with deletions in neurovirulence gene γ134.5: R3616, R849 (lacZ transgene), R3659 (alpha-tk), R8306 (murine IL-4 transgene), and R8308 (murine IL-10 transgene). The samples were taken from trigeminal ganglia and brains of BALB/c mice after corneal, intralabial, and intranasal infection, and the viral load was examined by viral culture, HSV DNA PCR, and VP16 reverse transcription (RT)-PCR. The results show that (i) intranasal infection was the most efficient means of spread to the central nervous system (CNS) besides intracranial injection; (ii) the viruses did not grow in the culture from the brain samples, but the viral DNA persisted even until day 21 postinfection; (iii) viral replication, as observed by VP16 mRNA RT-PCR, occurred mainly on days 4 and 7 postinfection in trigeminal ganglia and to a low extent in brain; (iv) R3659, R8306, and R8308 showed reactivation from the trigeminal ganglia in explant cultures; (v) in the brain, the vectors spread to the midbrain more efficiently than to other brain areas; and (vi) the deletions in the R3659 genome significantly limited the ability of this virus to replicate in the nervous system. The immunological studies show that (i) the only recombinant to induce IL-4 mRNA expression in the brain was R8306, the gamma interferon response was very low in the brain for R3659 and R8306, and the IL-23p19 response to R8306 decreased by day 21 postinfection, unlike for the other viruses; (ii) Δγ134.5 HSV vectors modulated the subsets of the splenocytes differently depending on the transgene; (iii) R3659 infection of the nervous system induces expression and production of cytokines from the stimulated splenocytes; and (iv) HSV vectors expressing IL-4 or IL-10 induce expression and production of both of the Th2-type cytokines from splenocytes. We conclude that the intranasal route of infection is a possible means of delivery of Δγ134.5 HSV vectors to the CNS in addition to intracranial infection, although replication in the CNS remains minimal. The DNA of the HSV vectors is able to reside in the brain for at least 3 weeks. The features of the immune response to the vectors must be considered and may be exploited in gene therapy experiments with these vectors.

scholarly journals Herpes Simplex Virus Type 1 at the Central Nervous System

Herpesviridae ◽  
10.5772/64130 ◽  
2016 ◽  
Author(s):  
Carola Otth ◽  
Francisca Acuña-Hinrichsen ◽  
Luis Leyton ◽  
Carolina Martin ◽  
Margarita I. Concha
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Herpes Simplex Virus ◽  
Herpes Simplex ◽  
Virus Type ◽  
Herpes Simplex Virus Type ◽  
The Central Nervous System ◽  
Simplex Virus
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