Richard B. Tenser

VARICELLA-ZOSTER VIRUS RNA IN HUMAN TRIGEMINAL GANGLIA

The technique of in situ hybridisation was used to examine human trigeminal ganglia for the presence of varicella-zoster virus (VZV) RNA. The ganglia were removed from fresh cadavers of individuals without a history of current or recent herpes zoster. Of the various types of cell in the ganglia, only the neurons appeared positive for VZV RNA. 0 to 0.3% of neurons were positive for VZV RNA.

Herpes simplex virus thymidine kinase expression in infection of the trigeminal ganglion.

Abstract Infection of the trigeminal ganglion was investigated using standard thymidine kinase-positive (TK + ) herpes simplex virus (HSV) and two TK − mutants. After corneal inoculation of mice with TK − HSV, the incidence of acute and latent trigeminal ganglion infection was markedly decreased compared to TK + virus. When cell-free virus was titered from mice 1 hr to 5 days post-corneal inoculation, ocular replication of TK − HSV was found to be similar to TK + HSV, but whereas TK + HSV replicated well and was found in substantial amounts in trigeminal ganglia (2 × 10 3 PFU/mg ganglion tissue), TK − HSV did not replicate in the ganglia. Mean TK − trigeminal ganglion virus titers were 10,000-fold less than TK + titers. When a TK + revertant of TK − mutant virus was tested, however, trigeminal ganglion virus replication was similar to that with the parental TK + virus. The results obtained were interpreted as being consistent with impaired axonal transport of TK − HSV from cornea to trigeminal ganglion neurons or more likely, with impaired replication of TK − HSV in ganglionic neurons.

Herpes simplex virus thymidine kinase expression in trigeminal ganglion infection: Correlation of enzyme activity with ganglion virus titer and evidence of in vivo complementation

Experimental trigeminal ganglion and corneal infection in mice was studied with three thymidine kinase-positive (TK+) strains of herpes simplex virus type 1 (HSV-1) and eight TK− HSV-1 mutants. Viruses were extensively tested in cell culture to determine whether any were temperature sensitive (ts) for virus replication or for TK activity. TK− mutants were no more ts than were TK+ viruses. By arabinosylthymine testing and measurement of thymidine phosphorylation, it was apparent that some TK− mutants were, in fact, intermediate for TK activity (TK±). After corneal inoculation of individual viruses it was observed with one exception that TK−, TK±, and TK+ viruses replicated in ocular tissues (3 days postinoculation, 2.2 × 103–1.1 × 105 PFU/eye). However, TK− mutants were rarely isolated from trigeminal ganglia ( 60–>1600). In addition, after inoculation of certain TK−–TK− pairs, complementation in ganglia was observed (complementation indices were >2.4–>120). These studies support the hypothesis that HSV-1 TK expression is necessary for sensory ganglion (neuron) infection in three ways: HSV-1 TK mutants that replicated in ocular tissues and were not ts mutants did not replicate in vivo in trigeminal ganglia; (ii) there was a correlation between level of viral TK activity and trigeminal ganglion virus titer; and (iii) when complemented by TK+ or TK− HSV, TK− virus replicated in trigeminal ganglia.

Trigeminal neuralgia Mechanisms of treatment

Background: Mechanisms of the surgical treatment of trigeminal neuralgia are considered. Results: Trigeminal neuralgia is effectively treated by microvascular decompression(MVD) and other surgical procedures. These procedures often cause reactivation of herpes simplex virus (HSV), which is latent in trigeminal ganglion neurons. Conclusion: MVD and other surgical procedures alter ganglion neuron transcription, as indicated by HSV reactivation. Controlled injury of the trigeminal root-ganglion probably occurs with the disparate surgical procedures, and this is likely the means of their effectiveness.

ROLE OF HERPES SIMPLEX VIRUS THYMIDINE KINASE EXPRESSION IN VIRAL PATHOGENESIS AND LATENCY

Herpes simplex virus (HSV) thymidine kinase (TK) expression and the HSV TK gene have been evaluated in studies of gene control, as well as in animal and human studies of viral pathogenesis, including HSV latency. In investigations of the biological role of HSV TK, enzyme expression was noted to be important for HSV infection of nonreplicating cells in culture; and, in experimental animal studies, HSV TK was shown to be important for in vivo latent infection of sensory ganglion neurons. Latency in these studies was determined by the ability of HSV to reactivate from sensory ganglion explants. In recent studies, investigators sought to determine whether the role HSV TK expression plays in latency is primarily in the establishment and maintenance of latency or in the reactivation process. Following infection of experimental animals with HSV TK-deficient mutants, the presence of HSV in ganglia was detected in complementation, rescue, and molecular biological studies. Results suggest that HSV TK expression may be important for HSV reactivation from latency. This was supported by in situ hybridization investigations. In the latter studies, HSV latency associated transcript (LAT) was present in ganglion neurons, although reactivation of HSV from such ganglia was defective. LAT-expressing, reactivation-defective infections established by TK mutants of HSV are considered examples of incomplete latency. From the present review, it appears that HSV TK expression, particularly TK expression of HSV-1, is important for the reactivation of latent HSV infection of sensory ganglion neurons, probably because of limited neuronal TK expression and absent replication capacity of these cells.

Inhibition of Herpes Simplex Virus Reactivation by Dipyridamole

ABSTRACT Herpes simplex virus (HSV) reactivation from latency was investigated. Reactivation of thymidine kinase-negative HSV, which is defective for reactivation, was greatly enhanced by thymidine (TdR). The reactivation-enhancing effect of TdR was blocked by dipyridamole (DPM), a known nucleoside transport inhibitor. DPM also inhibited wild-type HSV reactivation, suggesting potential antiviral use.

The role of pseudorabies virus thymidine kinase expression in trigeminal ganglion infection.

The role of pseudorabies virus (PRV) thymidine kinase (TK) expression in the pathogenesis of PRV infection of mice was studied with TK-negative (TK-) mutants. Thymidine phosphorylation and arabinosylthymine inhibition of PRV replication and efficiency of plating were used to characterize TK+ and TK- PRV. In addition, a plaque autoradiography procedure was utilized to determine the TK phenotype of individual plaques. TK+ and TK- PRV replicated well in ocular tissues, while TK+ but not TK- did so in ganglion tissue. Mortality was absent after TK- PRV inoculation and widespread after inoculation of similar amounts of TK+ PRV. Latent infection in mice was not detected with either TK+ or TK- PRV. This study indicated the probable importance of PRV TK expression in acute trigeminal ganglion infection.

Sequential changes of sensory neuron (fluoride-resistant) acid phosphatase in dorsal root ganglion neurons following neurectomy and rhizotomy

Five to seven days after sciatic nerve section in rats, fluoride-resistant acid phosphatase (FRAP) expression in dorsal root ganglion (drg) neurons was markedly decreased. The decrease was in contrast to increased acid phosphatase which has been reported to occur in other neurons after nerve section. FRAP expression in ganglion neurons subsequently increased 14-21 days after nerve section; this preceded the restitution of enzyme expression in the spinal cord substantia gelatinosa. FRAP expression in drg neurons was not decreased after dorsal root section.

Clinical significance of types of cerebellar amyloid plaques in human spongiform encephalopathies

We report three patients with both spongiform encephalopathy and cerebellar amyloid plaques; one showed kuru-like plaques and was diagnosed as having Creutzfeldt-Jakob disease (CJD), and two had multicentric plaques and were diagnosed as having Gerstmann-Sträussler-Scheinker disease (GSSD). Evaluation of these cases and review of others previously reported suggests a clinicopathologic correlation between type of cerebellar plaque and neurologic clinical course. CJD patients who showed kuru-like plaques generally had disease with early onset (average age, 49.1 years) and long duration (average, 34 months), as compared with CJD patients without kuru-like plaques. GSSD patients usually had multicentric cerebellar plaques, and cases were usually familial, had early age of onset (average, 42.7 years), and were of long duration (average, 73 months). Myoclonus was infrequent in GSSD patients and pathologically spongiform change was minimal; spinal tract degeneration was common.

Herpes simplex and herpes zoster. Nervous system involvement.

Mainly discussed are neurologic complications of two neurotropic herpesviruses: herpes simplex viruses types 1 and 2 and varicella-zoster virus. Briefly discussed are cytomegalovirus and Epstein-Barr virus. Treatment of immunosuppressed and nonimmunosuppressed patients is reviewed.