Detection of varicella‐zoster virus nucleic acid in neurons of normal human thoracic ganglia

Gilden, Donald H.; Rozenman, Yaacov; Murray, Ronald S.; Devlin, Mary; Vafai, Abbas

doi:10.1002/ana.410220315

Cited by 116 publications

(83 citation statements)

References 9 publications

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“…on May 12, 2018 by guest http://jcm.asm.org/ DISCUSSION We describe here, for the first time, persistent VZV DNA detection following a severe primary VZV infection in a seemingly immunocompetent child. During normal courses of varicella, VZV DNA is detectable in the first 2 weeks after the onset of varicella, after which the virus is cleared from blood, and develops latency in neurons of the dorsal root ganglia (19,28,30,36). VZV reactivation from latency is known as herpes zoster (shingles), which is limited to one or more dermatomes, as mostly observed in elderly patients or in patients taking immunosuppressive medication or may even generalize in severely immunocompromised patients.…”

Section: Virologymentioning

confidence: 99%

Persistent Detection of Varicella-Zoster Virus DNA in a Previously Healthy Child after Severe Chickenpox

et al. 2005

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In immunocompetent children with primary varicella-zoster virus (VZV) infection, peak viral loads are detected in peripheral blood near the onset of the vesicular rash. VZV DNA concentrations normally diminish and become undetectable within 3 weeks after the appearance of the exanthem. Here, we present a previously healthy, human immunodeficiency virus-negative, 4-year-old boy admitted with severe varicella. High viral loads (>340,000 copies/ml) were found in his blood, and the viral loads remained high for at least 1.5 years. Clinical recovery preceded complete clearance of the virus. General and VZV-specific immune reactivity were intact. NK cells and CD8؉ T cells were activated during acute infection, and VZV-specific CD4 ؉ T cells were detected at high frequencies. VZV DNA was initially detected in B cells, NK cells, and both CD4؉ and CD8 ؉ T cells. In contrast, during the persistent phase of VZV DNA detection, the viral DNA was primarily located in CD8 ؉ T cells. For the first time, we describe the persistent detection of VZV DNA in a previously healthy child.

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Section: Virologymentioning

confidence: 99%

Persistent Detection of Varicella-Zoster Virus DNA in a Previously Healthy Child after Severe Chickenpox

et al. 2005

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“…This is demonstrated by the reactivation of VZV in these individuals as herpes zoster and by the presence of VZV DNA and proteins in ganglia recovered at autopsy (2,3,5,9,10,12,13,15,16,19,20,(22)(23)(24)26). Different laboratories have ascribed the site of latency to either neurons (12-14, 18, 22) or perineuronal satellite cells (5,26); some laboratories suggest that neurons are the primary site of latency together with a smaller proportion of satellite cells containing the VZV genome (16,20).…”

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Varicella-Zoster Virus DNA in Cells Isolated from Human Trigeminal Ganglia

Levin

Cai

Manchak

et al. 2003

J Virol

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To determine the type of cell(s) that contain latent varicella-zoster virus (VZV) DNA, we prepared pure populations of neurons and satellite cells from trigeminal ganglia of 18 humans who had previously had a VZV infection. VZV DNA was present in 34 of 2,226 neurons (1.5%) and in none of 20,700 satellite cells. There was an average of 4.7 (range of 2 to 9) copies of VZV DNA per latently infected neuron. Latent VZV DNA was primarily present in large neurons, whereas the size distribution of herpes simplex virus DNA was markedly different.Varicella-zoster virus (VZV) is present in a latent form in sensory ganglia of humans who have had a primary infection (varicella) with VZV (11). This is demonstrated by the reactivation of VZV in these individuals as herpes zoster and by the presence of VZV DNA and proteins in ganglia recovered at autopsy (2,3,5,9,10,12,13,15,16,19,20,(22)(23)(24)26). Different laboratories have ascribed the site of latency to either neurons (12-14, 18, 22) or perineuronal satellite cells (5, 26); some laboratories suggest that neurons are the primary site of latency together with a smaller proportion of satellite cells containing the VZV genome (16,20). The primary aim of the experiments described here was to determine the type of cell in trigeminal ganglia that harbors latent VZV and also to obtain data on the proportion of these cells that contain latent VZV. One reason why the site of VZV latency has remained an open question is that neurons and satellite-supporting cells are tightly associated in ganglia and the in situ methods used to locate VZV DNA did not clearly resolve the source of the hybridization signal. This resolution was easier for latent HSV because a strong hybridization signal to HSV facilitated its localization to the nucleus of the neuron. In contrast, the hybridization signal from VZV DNA is considerably weaker and dispersed over both nucleus and cytoplasm. While the hybridization methodology has improved, these considerations remain (21, 30). To reduce the ambiguities inherent in the in situ methods, we developed a procedure to separate cell types prior to analysis. The separation procedure has been verified with a study of HSV (1). This report presents data on the cellular localization of latent VZV, the frequency of latency, and the number of viral genomes present in latent cells.

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“…However, in situ hybridization studies using VZV-specific probes have yielded conflicting data concerning the cellular location of the latent VZV and the prevalence of infected cells within these ganglia (8,10,12,13).…”

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Latency In Vitro of Varicella-Zoster Virus in Cells Derived from Human Fetal Dorsal Root Ganglia

et al. 1992

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ABSTRACT. A potential in vitvo model of varicella-zoster virus (VZV) latency was developed. Dissociated human dorsal root ganglion cultures were infected with VZV and maintained for 1 wk in the presence of bromovinyl arabinosy1 uracil, a potent inhibitor of VZV. Seven to 21 d after removing the inhibitor (214 d after infection), the cells were trypsinized, passed to monolayers of human embryonic lung fibroblasts, and observed for VZV reactivation as indicated by typical cytopathic effects and the appearance of VZV antigens. VZV reactivated from 56% of the cultures containing both neurons and satellite cells but not from cultures specifically enriched for either neurons, satellite cells, or ganglion-derived fibroblasts. The failure to isolate VZV from cell suspensions that were sonicated before cocultivation with fibroblasts indicated that infectious VZV was not present before reactivation. Moreover, immunohistochemical and immunoprecipitation studies revealed no VZV-specific antigens in any cultures before the reactivation stimulus. VZV antigens were detected after trypsinization and cocultivation. These findings suggest that cultures containing both neurons and satellite cells provide a model system for VZV persistence that possesses many properties of a latent infection. (Pediatr Res 32: 699-703,1992) Abbreviations VZV, varicella-zoster virus HSV, herpes simplex virus NGF, nerve growth factor HELF, human embryonic lung fibroblast CPE, cytopathic effect DRG, dorsal root ganglion DMEM, Dulbecco's modified essential medium EMEM, Eagle's minimal essential medium FUDR, fluorodeoxyuridine BVaraU, bromovinyl arabinosyl uracil pfu, plaque forming units VZV, which produces latent infection of human DRG during primary infection (varicella), can reactivate many years later to produce herpes zoster. The sites of latency were initially assumed to be the DRG and trigeminal ganglia, on the basis of the characteristic dermatomal distribution of herpes zoster (1-3) and the detection of VZV within the ganglia during the acute phase of herpes zoster (4, 5). However, numerous attempts to recover VZV from DRG and trigeminal ganglia of adult cadavers have all failed, in contrast to the frequent recovery of HSV from trigeminal and sacral ganglia (6, 7).These sites of VZV latency were established, finally, by detecting VZV nucleic acids in human ganglia harvested at autopsy from individuals who died without active infection (8-1 1). However, in situ hybridization studies using VZV-specific probes have yielded conflicting data concerning the cellular location of the latent VZV and the prevalence of infected cells within these ganglia (8,10,12,13).A model of VZV latency was approached in adult rats by S.C. paraspinous injection of virus and its subsequent detection in neurons by in situ hybridization. VZV was also reported to be reactivated from ganglion cells from these rats upon trypsinization and cocultivation with permissive fibroblasts (14). These findings seem surprising because the rat is not readily infected by VZV. Moreover...

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Detection of varicella‐zoster virus nucleic acid in neurons of normal human thoracic ganglia

Cited by 116 publications

References 9 publications

Persistent Detection of Varicella-Zoster Virus DNA in a Previously Healthy Child after Severe Chickenpox

Persistent Detection of Varicella-Zoster Virus DNA in a Previously Healthy Child after Severe Chickenpox

Varicella-Zoster Virus DNA in Cells Isolated from Human Trigeminal Ganglia

Latency In Vitro of Varicella-Zoster Virus in Cells Derived from Human Fetal Dorsal Root Ganglia

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