Varicella-Zoster Viruses Associated with Post-Herpetic Neuralgia Induce Sodium Current Density Increases in the ND7-23 Nav-1.8 Neuroblastoma Cell Line

Kennedy, Peter G. E.; Montague, Paul; Scott, Fiona; Grinfeld, Esther; Ashrafi, G. Hossein; Breuer, Judith; Rowan, Edward G.

doi:10.1371/journal.pone.0051570

Cited by 39 publications

(50 citation statements)

References 36 publications

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“…Our present results also confirm that infection of differentiated ND7-23 cells with HSV-1 also causes a significant reduction in the Na + current densities. However, infection of ND7 cells with the varicella-zoster herpes virus that causes chickenpox results in a significant increase in Na + current densities (Kennedy et al, 2013). Thus, herpes viral infection can have various effects on ion channel expression.…”

Section: Discussionmentioning

confidence: 99%

Regulation of T-type Ca2+ channel expression by herpes simplex virus-1 infection in sensory-like ND7 cells

2017

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Infection of sensory neurons by herpes simplex virus (HSV)-1 disrupts electrical excitability, altering pain sensory transmission. Because of their low threshold for activation, functional expression of T-type Ca2+ channels regulates various cell functions, including neuronal excitability and neuronal communication. In this study, we have tested the effect of HSV-1 infection on the functional expression of T-type Ca2+ channels in differentiated ND7-23 sensory-like neurons. Voltage-gated Ca2+ currents were measured using whole cell patch clamp recordings in differentiated ND7-23 neurons under various culture conditions. Differentiation of ND7-23 cells evokes a significant increase in T-type Ca2+ current densities. Increased T-type Ca2+ channel expression promotes the morphological differentiation of ND7-23 cells and triggers a rebound depolarization. HSV-1 infection of differentiated ND7-23 cells causes a significant loss of T-type Ca2+ channels from the membrane. HSV-1 evoked reduction in the functional expression of T-type Ca2+ channels is mediated by several factors, including decreased expression of Cav3.2 T-type Ca2+ channel subunits and disruption of endocytic transport. Decreased functional expression of T-type Ca2+ channels by HSV-1 infection requires protein synthesis and viral replication, but occurs independently of Egr-1 expression. These findings suggest that infection of neuron-like cells by HSV-1 causes a significant disruption in the expression of T-type Ca2+ channels, which can results in morphological and functional changes in electrical excitability.

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Section: Discussionmentioning

confidence: 99%

Regulation of T-type Ca2+ channel expression by herpes simplex virus-1 infection in sensory-like ND7 cells

2017

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“…We suspect that transcription of VZV genes within virus-infected neurons may themselves lead to the chronic pain state either through induction of inflammatory mechanisms or through expression of proteins, such as transcriptional regulators, that may alter host cell expression patterns. 11,43,44 Studies are ongoing to determine whether viral transactivators, IE62 and IE63, are required for the induction of the chronic pain state.…”

Section: Discussionmentioning

confidence: 99%

Relief of pain induced by varicella-zoster virus in a rat model of post-herpetic neuralgia using a herpes simplex virus vector expressing enkephalin

et al. 2014

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Acute and chronic pain (post-herpetic neuralgia or PHN) are encountered in patients with herpes zoster that is caused by reactivation of varicella-zoster virus (VZV) from a state of neuronal latency. PHN is often refractory to current treatments, and additional strategies for pain relief are needed. Here we exploited a rat footpad model of PHN to show that herpes simplex virus (HSV) vector-mediated gene delivery of human preproenkephalin (vHPPE) effectively reduced chronic VZV-induced nocifensive indicators of pain. VZV inoculated at the footpad induced prolonged mechanical allodynia and thermal hyperalgesia that did not develop in controls or with ultraviolet light-inactivated VZV. Subsequent footpad administration of vHPPE relieved VZV-induced pain behaviors in a dose-dependent manner for extended periods, and prophylactic vector administration prevented VZV-induced pain from developing. Short-term pain relief following low-dose vHPPE administration could be effectively prolonged by vector re-administration. HPPE transcripts were increased three- to fivefold in ipsilateral ganglia, but not in the contralateral dorsal root ganglia. VZV hypersensitivity and its relief by vHPPE were not affected by peripheral delivery of opioid receptor agonist or antagonist, suggesting that the efficacy was mediated at the ganglion and/or spinal cord level. These results support further development of ganglionic expression of enkephalin as a novel treatment for the pain associated with Zoster.

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“…Recently, certain strains of VZV were postulated to produce PHN by altering voltage-gated sodium channels, leading to altered excitability 66,67 . Isolated and then cultured VZV strains from patients with PHN and those with zoster but without PHN were applied to neuroblastoma cells that express fast and slow sodium channels.…”

Section: Mechanisms/pathophysiologymentioning

confidence: 99%

Varicella zoster virus infection

Gershon

Breuer

Cohen

et al. 2015

Nat Rev Dis Primers

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535

531

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Infection with varicella zoster virus (VZV) causes varicella (chickenpox), which can be severe in immunocompromised individuals, infants and adults. Primary infection is followed by latency in ganglionic neurons. During this period, no virus particles are produced and no obvious neuronal damage occurs. Reactivation of the virus leads to virus replication, which causes zoster (shingles) in tissues innervated by the involved neurons, inflammation and cell death — a process that can lead to persistent radicular pain (postherpetic neuralgia). The pathogenesis of postherpetic neuralgia is unknown and it is difficult to treat. Furthermore, other zoster complications can develop, including myelitis, cranial nerve palsies, meningitis, stroke (vasculopathy), retinitis, and gastroenterological infections such as ulcers, pancreatitis and hepatitis. VZV is the only human herpesvirus for which highly effective vaccines are available. After varicella or vaccination, both wild-type and vaccine-type VZV establish latency, and long-term immunity to varicella develops. However, immunity does not protect against reactivation. Thus, two vaccines are used: one to prevent varicella and one to prevent zoster. In this Primer we discuss the pathogenesis, diagnosis, treatment, and prevention of VZV infections, with an emphasis on the molecular events that regulate these diseases. For an illustrated summary of this Primer, visit: http://go.nature.com/14×VI1

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Varicella-Zoster Viruses Associated with Post-Herpetic Neuralgia Induce Sodium Current Density Increases in the ND7-23 Nav-1.8 Neuroblastoma Cell Line

Cited by 39 publications

References 36 publications

Regulation of T-type Ca2+ channel expression by herpes simplex virus-1 infection in sensory-like ND7 cells

Regulation of T-type Ca2+ channel expression by herpes simplex virus-1 infection in sensory-like ND7 cells

Relief of pain induced by varicella-zoster virus in a rat model of post-herpetic neuralgia using a herpes simplex virus vector expressing enkephalin

Varicella zoster virus infection

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