A Common Neuronal Response to Alphaherpesvirus Infection

Szpara, Moriah L.; Kobiler, Oren; Enquist, Lynn W.

doi:10.1007/s11481-010-9212-0

Cited by 37 publications

(40 citation statements)

References 56 publications

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“…However, there is a precedent for a herpes virus (Herpes simplex virus-1) latency-associated transcript (LAT) influencing the accumulation of host cell transcripts encoding apoptotic regulatory proteins [36], so an analogous mechanism may be relevant here. While we did not detect VZV proteins in our system, it should be noted that alphaherpes viruses, including VZV and herpes simplex virus (HSV) can lead to a common neuronal response resulting in numerous gene expression changes in ganglia [37]. Further, HSV-1 latency-associated transcript infection of cultured trigeminal neurons results in increased levels of the neuropeptide Substance P which is known to be associated with neuropathic pain [38] and sodium ion channel proteins have been detected in the rat VZV pain model [15].…”

Section: Discussionmentioning

confidence: 60%

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

et al. 2013

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Post-herpetic neuralgia (PHN) is the most significant complication of herpes zoster caused by reactivation of latent Varicella-Zoster virus (VZV). We undertook a heterologous infection in vitro study to determine whether PHN-associated VZV isolates induce changes in sodium ion channel currents known to be associated with neuropathic pain. Twenty VZV isolates were studied blind from 11 PHN and 9 non-PHN subjects. Viruses were propagated in the MeWo cell line from which cell-free virus was harvested and applied to the ND7/23-Nav1.8 rat DRG x mouse neuroblastoma hybrid cell line which showed constitutive expression of the exogenous Nav 1.8, and endogenous expression of Nav 1.6 and Nav 1.7 genes all encoding sodium ion channels the dysregulation of which is associated with a range of neuropathic pain syndromes. After 72 hrs all three classes of VZV gene transcripts were detected in the absence of infectious virus. Single cell sodium ion channel recording was performed after 72 hr by voltage-clamping. PHN-associated VZV significantly increased sodium current amplitude in the cell line when compared with non-PHN VZV, wild-type (Dumas) or vaccine VZV strains ((POka, Merck and GSK). These sodium current increases were unaffected by acyclovir pre-treatment but were abolished by exposure to Tetrodotoxin (TTX) which blocks the TTX-sensitive fast Nav 1.6 and Nav 1.7 channels but not the TTX-resistant slow Nav 1.8 channel. PHN-associated VZV sodium current increases were therefore mediated in part by the Nav 1.6 and Nav 1.7 sodium ion channels. An additional observation was a modest increase in message levels of both Nav1.6 and Nav1.7 mRNA but not Nav 1.8 in PHN virally infected cells.

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Section: Discussionmentioning

confidence: 60%

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

et al. 2013

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“…Alternatively, host proteins may be included in virions nonspecifically, and their presence could reflect proteins that are highly abundant within the cell or enriched at sites of viral assembly. Although little is known about the copy numbers of host proteins in mock-and PRV-infected PK15 cells, several studies have investigated the expression of host genes in a variety of PRV-and HSV-1-infected cell types and tissues (115,129). Interestingly, the mRNA expression levels corresponding to 9 of the 48 cellular proteins we detected were decreased more than 3-fold during PRV infection of rat embryonic fibroblasts (115).…”

Section: Vol 85 2011 Proteomic Analysis Of Prv Virions 6437mentioning

confidence: 84%

Proteomic Characterization of Pseudorabies Virus Extracellular Virions

Kramer

Greco

Enquist

et al. 2011

J Virol

131

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Pseudorabies virus (PRV), a member of the Alphaherpesvirinae, has a complex multilayered extracellular virion that is structurally conserved among other herpesviruses. PRV virions contain a double-stranded DNA genome within a proteinaceous capsid surrounded by the tegument, a layer of viral and cellular proteins. The envelope layer, which encloses the capsid and tegument, contains viral transmembrane proteins anchored in a phospholipid bilayer. The viral and host proteins contained within virions execute important functions during viral spread and pathogenesis, but a detailed understanding of the composition of PRV virions has been lacking. In this report, we present the first comprehensive proteomic characterization of purified PRV virions by mass spectrometry using two complementary approaches. To exclude proteins present in the extracellular medium that may nonspecifically associate with virions, we also analyzed virions treated with proteinase K and samples prepared from mock-infected cells. Overall, we identified 47 viral proteins associated with PRV virions, 40 of which were previously localized to the capsid, tegument, and envelope layers using traditional biochemical approaches. Additionally, we identified seven viral proteins that were previously undetected in virions, including pUL8, pUL20, pUL32, pUL40 (RR2), pUL42, pUL50 (dUTPase), and Rsp40/ICP22. Furthermore, although we did not enrich for posttranslational modifications, we detected phosphorylation of four virion proteins: pUL26, pUL36, pUL46, and pUL48. Finally, we identified 48 host proteins associated with PRV virions, many of which have known functions in important cellular pathways such as intracellular signaling, mRNA translation and processing, cytoskeletal dynamics, and membrane organization. This analysis extends previous work aimed at determining the composition of herpesvirus virions and provides novel insights critical for understanding the mechanisms underlying PRV entry, assembly, egress, spread, and pathogenesis.Pseudorabies virus (PRV) is a swine alphaherpesvirus closely related to the human pathogens herpes simplex virus type 1 and 2 (HSV-1 and HSV-2) and varicella-zoster virus (VZV) (96,113). PRV is a pantropic, neuroinvasive virus with a broad host range and has been used extensively as a powerful tool for studying the architecture of mammalian neuronal circuits (35). The infectious particle of PRV, known as the mature virion, is a multilayered structure that is conserved among all herpesvirus families. At the core of the virion is a linear doublestranded DNA genome that is packaged within a proteinaceous capsid. The capsid is surrounded by a layer of viral and cellular proteins known as the tegument, which is enclosed within a phospholipid bilayer studded with viral transmembrane proteins and is known as the virion envelope (96, 113). To understand the fundamental mechanisms underlying PRV spread and pathogenesis, a comprehensive understanding of the subunits that compose the highly complex virion structure is necessary.The ini...

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“…Unlike epithelial cells, PNS neurons produce little type I interferon (IFN) after HSV-1 infection (22,23). Nevertheless, prior to, or concurrent with, invasion by herpes virus virions, nerve terminals are bathed in a variety of inflammatory and antiviral cytokines, including type I IFN (IFN-␣ and IFN-␤) and type III IFN (IFN-), produced by other surrounding infected cells (8).…”

Section: Axons Have a Noncanonical Interferon Responsementioning

confidence: 99%

Intrinsic and Innate Defenses of Neurons: Détente with the Herpesviruses

Enquist

Leib

2017

J Virol

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Neuroinvasive herpesviruses have evolved to efficiently infect and establish latency in neurons. The nervous system has limited capability to regenerate, so immune responses therein are carefully regulated to be nondestructive, with dependence on atypical intrinsic and innate defenses. In this article we review studies of some of these noncanonical defense pathways and how herpesvirus gene products counter them, highlighting the contributions that primary neuronal in vitro models have made to our understanding of this field.

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A Common Neuronal Response to Alphaherpesvirus Infection

Cited by 37 publications

References 56 publications

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

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

Proteomic Characterization of Pseudorabies Virus Extracellular Virions

Intrinsic and Innate Defenses of Neurons: Détente with the Herpesviruses

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