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Neuronal changes induced by Varicella Zoster Virus in a rat model of Post Herpetic Neuralgia

ABSTRACT: Neuronal reactivation of latent varicella zoster virus (VZV) causes debilitating and protracted pain (post herpetic neuralgia: PHN) in a significant fraction of patients. Productive infection of VZV seems to occur only in humans and primates, so VZV-infected human cells (e.g., MEWO cell line) are used to transmit VZV to rodents. A commonly accepted method of assessing nociception is ipsilateral nocifensive (pain avoidance) behavior in rats which have been injected in a footpad. No such behavioral change is associated with the contralateral (uninjected) footpad. Uninfected MEWO cells or VZV-infected MEWO cells were inoculated into the glabrous region of the right rear footpad of male Sprague-Dawley rats. By 9 days post-inoculation, there was a VZV-dependent decrease in the frequency of neurites that extend from the dermis past the stratum basale layer of the footpad epidermis. Between 7 days and 21 days post-inoculation there was a VZV-dependent increase in nocifensive behaviours in the rats. All VZV-dependent effects occurred in the absence of the productive VZV infection. That is, the virus entered rodent cells and expressed immediate early and early genes, but did not express late genes, synthesize viral DNA, or release infectious virions. Animals which had developed VZV-dependent nocifensive behaviours at 10 days were euthanized, and dorsal root ganglia (L4,5) ipsilateral to inoculation were taken for microarray analysis. Dorsal root ganglia from matching control animals were also analyzed.

ORGANISM(S): Rattus norvegicus

PROVIDER: GSE64345 | GEO | 2015/03/31

SECONDARY ACCESSION(S): PRJNA270777

REPOSITORIES: GEO

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Neuronal changes induced by Varicella Zoster Virus in a rat model of Post Herpetic Neuralgia

Project description:Neuronal reactivation of latent varicella zoster virus (VZV) causes debilitating and protracted pain (post herpetic neuralgia: PHN) in a significant fraction of patients. Productive infection of VZV seems to occur only in humans and primates, so VZV-infected human cells (e.g., MEWO cell line) are used to transmit VZV to rodents. A commonly accepted method of assessing nociception is ipsilateral nocifensive (pain avoidance) behavior in rats which have been injected in a footpad. No such behavioral change is associated with the contralateral (uninjected) footpad. Uninfected MEWO cells or VZV-infected MEWO cells were inoculated into the glabrous region of the right rear footpad of male Sprague-Dawley rats. By 9 days post-inoculation, there was a VZV-dependent decrease in the frequency of neurites that extend from the dermis past the stratum basale layer of the footpad epidermis. Between 7 days and 21 days post-inoculation there was a VZV-dependent increase in nocifensive behaviours in the rats. All VZV-dependent effects occurred in the absence of the productive VZV infection. That is, the virus entered rodent cells and expressed immediate early and early genes, but did not express late genes, synthesize viral DNA, or release infectious virions. Animals which had developed VZV-dependent nocifensive behaviours at 10 days were euthanized, and dorsal root ganglia (L4,5) ipsilateral to inoculation were taken for microarray analysis. Dorsal root ganglia from matching control animals were also analyzed. Control (uninfected MEWO cells) or VZV-infected MEWO cells were inoculated into the glabrous region of the right rear footpad of male Sprague-Dawley rats. After development of ipsilateral nocifensive behaviour in the VZV-infected animals, the ipsilateral dorsal root ganglia (L4,5) from infected and control animals were taken for microarray analysis.

2015-03-31 | E-GEOD-64345 | biostudies-arrayexpress

Comprehensive Analysis of Transcriptome in Dorsal Root Ganglia Following Chronic Constriction Injury.

Project description:To investigate mechanisms underlying neuropathic pain, we established sciatic nerve chronic constriction injury (CCI) neuropathic pain model in rats, and performed RNA-seq on ipsilateral bulk L4-L6 dorsal root ganglia from CCI rats and sham rats 11 days after surgery. By comprehensive analysis, we identified several key mRNAs and miRNAs, especially those associated with inflammatory immune response, may serve as promising targets, facilitating further investigation and eventually developing better therapeutic strategies for NP.

2023-03-15 | GSE212311 | GEO

Human melanoma MeWo cell phosphopeptide enriched Orbitrap MS

Project description:Our newly developed high-throughput screening assay of bioactive compounds discovered a cellular phosphatase, calcineurin, was critical in the regulation of Varicella-Zoster Virus (VZV) glycoprotein complex gB/gH-gL mediated cell fusion. To better understand how calcineurin regulates fusion, the potential substrates for calcineurin phosphatase were investigated in human melanoma MeWo cells upon treatment with specific calcineurin phosphatase inhibitor, pimecrolimus. Phosphopeptide enrichment and Orbitrap mass spectrometry analysis identified seven proteins that were exclusively phosphorylated in MeWo cells treated with pimecrolimus compared to DMSO vehicle control, including two known calcineurin substrates. The other five proteins were novel targets for calcineurin dephosphorylation. These data implicated that one or more of these seven proteins in the calcineurin mediated regulation of VZV gB/gH-gL mediated cell fusion.

2020-10-23 | PXD018290 | Pride

Postoperative pain and dorsal root ganglia transcriptomic signatures in a novel rat model of total knee arthroplasty

Project description:These data are from a preclinical model of total knee arthroplasty (TKA) performed in healthy rats. One day after surgery, ipsilateral dorsal root ganglia (DRG) from L3 and L4 were collected for RNA extraction and sequencing.

2022-03-23 | GSE195833 | GEO

Interferon-induced transmembrane protein 1 (IFITM1) inhibits Varicella-Zoster Virus Replication

Project description:Hosts have evolved numerous mechanisms to prevent primary viral infections. Interferon signaling is an important host defense mechanism against primary infection. Interferon gamma (IFN-γ) is a potent cytokine produced following primary varicella-zoster virus (VZV) infection. Furthermore, VZV reactivation correlates with a decline in IFN-γ-producing immune cells. Our previous results showed that pretreatment with 20 ng/ml of IFN-γ completely inhibited VZV replication in lung fibroblast MRC-5 and retinal epithelial ARPE-19, suggesting that IFN-γ-stimulated protein(s) inhibit viral replication. Our microarray analysis revealed that a small subset of interferon-stimulated genes (ISGs) was upregulated by greater than 3.5-fold at 8 h post-treatment in both ARPE-19 and MRC-5 cells compared to those of melanoma MeWo cells. The depletion of IFITM1 and IRF1 by siRNA in IFN-γ-treated cells significantly increased (from 0 to ~1x103 pfu/105 cells) VZV yields. In contrast, the depletion of a nontargeting control (siNTC) did not increase virus yield. Ectopic expression of interferon-induced transmembrane protein 1 (IFITM1) reduced the level of IE62 protein as well as intracellular VZV yield in both ARPE-19 and MeWo cells, but did not reduce the expression level of IE62 mRNA, suggesting that IFITM1 expression reduces the expression level of IE62 by post-transcriptional regulation. IFITM1 also reduced the expression levels of VZV IE62, HSV-1 ICP4, and EHV-1 IEP in ARPE-19 cells

2021-01-20 | GSE165112 | GEO

Lack of strong innate immune reactivity renders macrophages alone unable to control productive Varicella-Zoster Virus infection in an isogenic human iPSC-derived neuronal co-culture model.

Project description:With Varicella-Zoster Virus (VZV) being an exclusive human pathogen, human induced pluripotent stem cell (hiPSC)-derived neural cell culture models are an emerging tool to investigate VZV neuro-immune interactions. Using a compartmentalized hiPSC-derived neuronal model allowing axonal VZV infection, we previously demonstrated that paracrine interferon (IFN)-α2 signalling is required to activate a broad spectrum of interferon-stimulated genes able to counteract a productive VZV infection in hiPSC-neurons. In this new study, we now investigated whether innate immune signalling by VZV-challenged macrophages was able to orchestrate an antiviral immune response in VZV-infected hiPSC-neurons. In order to establish an isogenic hiPSC-neuron / hiPSC-macrophage co-culture model, hiPSC-macrophages were generated and characterised for phenotype, gene expression, cytokine production and phagocytic capacity. Even though immunological competence of hiPSC-macrophages was shown following stimulation with the VZV mimic poly(dA:dT) or treatment with IFN-α2, hiPSC-macrophages in co-culture with VZV-infected hiPSC-neurons were unable to mount an antiviral immune response capable of suppressing a productive neuronal VZV infection. Subsequently, a comprehensive RNA-Seq analysis confirmed the lack of strong immune responsiveness by hiPSC-neurons and hiPSC-macrophages upon, respectively, VZV infection or challenge. This may suggest the need of other cell types, like T-cells or other innate immune cells, to (co-)orchestrate an efficient antiviral immune response against VZV-infected neurons.

2023-04-19 | GSE228390 | GEO

Transcriptome analysis of dorsal root ganglion in rats with knee rheumatoid arthritis

Project description:To determine the LncRNA expression profile in dorsal root ganglia tissues of 7 days after rats received 150 μl of CFA (1 mg/ml Mycobacterium tuberculosis, Sigma, USA) through the patella tendon into the right knee joint. CFA injection rats macthed saline injection rats, we uesed LncRNA microArray analysis form Arraystar to examine the expression of LncRNAs and mRNAs in dorsal root ganglia tissues of 7 days after rats received CFA through the patella tendon into the right knee joint and matched Saline through the patella tendon into the right knee joint.

2020-11-12 | GSE146881 | GEO

Increased gene expression in the peridontium of unopposed molars in rats

Project description:The crowns of the right maxillary molars were removed in 28 days old male Wistar rats (experimental). Gene expression patterns were examined in the periodontal ligaments (PDLs) of the ipsilateral and contralateral mandibular molars, three and fifteen days later. Rats whith no dental interventions served as controls. We used microarrays to detail gene expression underlying post-emergent tooth eruption and identified distinct classes of up-regulated genes during this process.

2016-11-01 | GSE80965 | GEO

Gene activity induced by denervation in the rat urinary bladder [mRNA]

Project description:Bilateral freezing of the pelvic ganglia in female rats were performed to denervate the urinary bladder. Sham operated rats were used as controls. The rats were sacrificed 10 days after surgery. The urinary bladders (including the urothelium) were frozen and used for RNA extraction.

2018-03-10 | GSE104538 | GEO

Gene activity induced by denervation in the rat urinary bladder [miRNA]

2018-03-10 | GSE104539 | GEO

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