Herpes Simplex Associated with Trigeminal Neuralgia

Behrman, Simon; Knight, Geoffrey

doi:10.1212/wnl.4.7.525

Cited by 44 publications

(7 citation statements)

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“…Alternatively, the viral antigens, which were observed in necrotic cells, may be the result of secondary viral reactivation occurring subsequent to infarction. Studies have shown that a loss of connection between a sensory ganglion and the central nervous system results in HSV reactivation (37)(38)(39)(40)(41); thus, it is possible that by disrupting the architecture and function of the ganglion, necrosis triggers viral reactivation.…”

Section: Discussionmentioning

confidence: 99%

Analysis of T Cell Responses during Active Varicella-Zoster Virus Reactivation in Human Ganglia

Steain

Sutherland

Rodriguez

et al. 2014

J Virol

104

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Varicella-zoster virus (VZV) is responsible for both varicella (chickenpox) and herpes zoster (shingles). During varicella, the virus establishes latency within the sensory ganglia and can reactivate to cause herpes zoster, but the immune responses that occur in ganglia during herpes zoster have not previously been defined. We examined ganglia obtained from individuals who, at the time of death, had active herpes zoster. Ganglia innervating the site of the cutaneous herpes zoster rash showed evidence of necrosis, secondary to vasculitis, or localized hemorrhage. Despite this, there was limited evidence of VZV antigen expression, although a large inflammatory infiltrate was observed. Characterization of the infiltrating T cells showed a large number of infiltrating CD4؉ T cells and cytolytic CD8 ؉ T cells. Many of the infiltrating T cells were closely associated with neurons within the reactivated ganglia, yet there was little evidence of T cell-induced neuronal apoptosis. Notably, an upregulation in the expression of major histocompatibility complex class I (MHC-I) and MHC-II molecules was observed on satellite glial cells, implying these cells play an active role in directing the immune response during herpes zoster. This is the first detailed characterization of the interaction between T cells and neuronal cells within ganglia obtained from patients suffering herpes zoster at the time of death and provides evidence that CD4؉ and cytolytic CD8 ؉ T cell responses play an important role in controlling VZV replication in ganglia during active herpes zoster. IMPORTANCEVZV is responsible for both varicella (chickenpox) and herpes zoster (shingles). During varicella, the virus establishes a life-long dormant infection within the sensory ganglia and can reawaken to cause herpes zoster, but the immune responses that occur in ganglia during herpes zoster have not previously been defined. We examined ganglia obtained from individuals who, at the time of death, had active herpes zoster. We found that specific T cell subsets are likely to play an important role in controlling VZV replication in ganglia during active herpes zoster.

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Section: Discussionmentioning

confidence: 99%

Analysis of T Cell Responses during Active Varicella-Zoster Virus Reactivation in Human Ganglia

Steain

Sutherland

Rodriguez

et al. 2014

J Virol

104

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“…These conditions are usually a result of injury or disease of one or more nerve roots of the trigeminal ganglion. Possible causes include nerve trauma [1], compression of the trigeminal nerve root as in trigeminal neuralgia [2], demyelinating disorders, such as multiple sclerosis [3], neoplastic infiltration [4], and familial disorders, such as Charcot-Marie-Tooth disease [5], and secondary to herpetic infections [6]. In many cases, the cause of the neuropathic changes are not understood, however it has been suggested that dysfunction of both peripheral or central nervous systems may contribute [2,7,8].…”

Section: Introductionmentioning

confidence: 99%

Pathological Mechanisms and Therapeutic Targets for Trigeminal Neuropathic Pain

Bista

Imlach

2019

Medicines

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Trigeminal neuropathic pain is a chronic pain condition caused by damage or inflammation of the trigeminal nerve or its branches, with both peripheral and central nervous system dysfunction contributing to the disorder. Trigeminal pain conditions present with diagnostic and therapeutic challenges to healthcare providers and often require multiple therapeutic approaches for pain reduction. This review will provide the overview of pathophysiology in peripheral and central nociceptive circuits that are involved in neuropathic pain conditions involving the trigeminal nerve and the current therapeutics that are used to treat these disorders. Recent advances in treatment of trigeminal pain, including novel therapeutics that target ion channels and receptors, gene therapy and monoclonal antibodies that have shown great promise in preclinical studies and clinical trials will also be described.

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“…In brief, latent virus reactivates and is readily demonstrable in trigeminal ganglia excised from mice and explanted in appropriate medium at least 28 d after virus inoculation by the corneal route. The relevance of this protocol for the study of reactivation dates back to the pioneering studies by Cushing (8) and others (9)(10)(11)(12) showing that in patients suffering from trigeminal neuralgia the severance of the connection between the ganglion and the brain results in virus reactivation and atrophy of the ganglion. Extraction of ganglia failed to yield infectious virus (9).…”

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confidence: 99%

HSV-1 gene expression from reactivated ganglia is disordered and concurrent with suppression of latency-associated transcript and miRNAs

Zhou

Roizman

2011

Proc. Natl. Acad. Sci. U.S.A.

110

132

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In cell cultures, HSV-1 replication is initiated by recruitment by virion protein 16 of transcriptional factors and histone-modifying enzymes to immediate early (α) gene promoters. HSV establishes latent infections characterized by suppression of viral gene expression except for latency-associated transcripts (LATs) and miRNAs. The latent virus reactivates in stressed neurons. A fundamental question is how reactivation initiates in the absence of virion protein 16. We report the following findings in the ganglion explant model. (i) Anti-nerve growth factor antibody accelerated the reactivation of latent virus. Viral mRNAs were detected as early as 9 h after explantation. (ii) After explantation the amounts of viral mRNAs increased whereas amounts of miRNAs and LATs decreased. The decrease in miRNAs and LATs required ongoing protein synthesis, raising the possibility that LAT and miRNAs were degraded by a viral gene product. (iii) The expression of viral genes in explanted ganglia was disordered rather than sequentially ordered as in infected cells in culture. These findings suggest that in reactivating ganglia gene expression is totally derepressed and challenge the current models in that establishment of or exit from latency could not be dependent on the suppression or activation of single or small clusters of viral genes. Finally, miRNAs and LATs reached peak levels 9-11 d after corneal inoculation, thus approximating the pattern of virus replication in these ganglia. These findings suggest that the patterns of accumulation of LATs and miRNAs reflect many different stages in the infection of neurons.T o initiate infection in cell culture and presumably also at the portal of entry into the body, the HSV-1 capsid delivers the DNA to the nucleus. Concurrently, virion protein 16 (VP16), a key viral protein packaged in the virion and delivered to the nucleus, recruits the cellular factors octamer-binding protein 1 (Oct1), host cell factor 1 (HCF1), lysine-specific demethylase 1 (LSD1), circadian locomotor output cycles kaput (CLOCK) histone acetyl transferase, and other transcriptional factors to initiate a cascade of viral gene expression that begins with immediate early (α) genes followed by early (β) and late (γ) genes (1-5). VP16 is encoded by a γ gene expressed late in infection (1). In all, the transcriptional program yields almost 100 different transcripts. In contrast, in latently infected neurons viral gene expression is limited to the latency-associated transcript (LAT) and approximately six or more miRNAs (6, 7). Given the requirement for VP16 to initiate viral replication in productively infected cells, the question arises as to how virus replication initiates in stressed neurons harboring latent virus. Among the many hypotheses, two stand out: That VP16 is expressed first or that in neurons α gene expression can ensue in the absence of VP16.Resolution of this problem requires analyses of the reactivation in ganglia under conditions that are physiologically similar to those that occur in vivo. In the st...

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Herpes Simplex Associated with Trigeminal Neuralgia

Cited by 44 publications

References 0 publications

Analysis of T Cell Responses during Active Varicella-Zoster Virus Reactivation in Human Ganglia

Analysis of T Cell Responses during Active Varicella-Zoster Virus Reactivation in Human Ganglia

Pathological Mechanisms and Therapeutic Targets for Trigeminal Neuropathic Pain

HSV-1 gene expression from reactivated ganglia is disordered and concurrent with suppression of latency-associated transcript and miRNAs

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