Transcriptome Analysis Reveals the Role of Cellular Calcium Disorder in Varicella Zoster Virus-Induced Post-Herpetic Neuralgia

Wu, Songbin; Yang, Shaomin; Ou, Mingxi; Chen, Jiamin; Huang, Jinbo; Xiong, Dehua; Sun, Wuping; Xiao, Lizu

doi:10.3389/fnmol.2021.665931

Cited by 18 publications

(16 citation statements)

References 59 publications

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“…However, such association for POLR3 subtypes D or GL have not been described so far. Furthermore, a recent report in which the involvement of cellular calcium disorder in the development of PHN was investigated, revealed several DEGs [46]. Voltage-gated and ligand-gated calcium channels in neurons play an important role in the regulation of Ca 2+ influx in neurons and glia of the CNS [47].…”

Section: Discussionmentioning

confidence: 99%

Unraveling the immune signature of herpes zoster: Insights into pathophysiology and the HLA risk profile

Vandoren

Boeren

Shippers

et al. 2023

Preprint

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The varicella-zoster virus (VZV) infects over 95% of the population and establishes latency afterwards. Reactivation of VZV causes herpes zoster (HZ), commonly known as shingles, which presents as a painful rash in mostly the elderly and people with a weakened immune system. However, HZ might occur in otherwise healthy individuals too. In this study, we have studied the immune signature of HZ to better understand HZ's pathophysiology. We provide a general overview of the antiviral state and the activation of innate and adaptive immune responses during HZ. Differential gene expression and gene ontology analyses revealed upregulation of several genes and host immune pathways during herpes zoster, especially related to type I IFN response but also related to adaptive immune responses. Intriguingly, no differences in gene expression were noted during convalescence between HZ patients and controls. Furthermore, we conducted the largest HLA association study on HZ to date using the UK Biobank and identified seven protective and four risk HLA alleles associated with the development of herpes zoster. These findings reveal key genes and pathways involved in the host immune response to symptomatic VZV reactivation and provide new molecular insights into the development of HZ.

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Section: Discussionmentioning

confidence: 99%

Unraveling the immune signature of herpes zoster: Insights into pathophysiology and the HLA risk profile

Vandoren

Boeren

Shippers

et al. 2023

Preprint

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“…These calcium channels and receptors have been reported to be involved in pain and neuroplasticity associated with chronic pain states ( 35 ). In particular, our previous studies have shown that VZV infection could cause cellular calcium signal disorders manifested by significant changes in the expression of calcium signal-related genes and abnormalities in the distribution and content of calcium ions in cells ( 37 ). All the evidence implied that VZV-mediated abnormal expression and/or dysfunction of cellular calcium channels and receptors might be an important factor in the onset and maintenance of PHN.…”

Section: Discussionmentioning

confidence: 99%

Change in Cav3.2 T-Type Calcium Channel Induced by Varicella-Zoster Virus Participates in the Maintenance of Herpetic Neuralgia

Yang

et al. 2021

Front. Neurol.

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Pain, as the most prevalent neurological complication of herpes zoster (HZ), may occur before or during the rash onset or even after the rash has recovered. Particularly, postherpetic neuralgia (PHN) is a refractory chronic condition, usually defined as pain persisting for 3 months or longer from the onset of HZ. Pain evoked by HZ impairs the normal physical and emotional functions of the patients, severely reducing their quality of life. However, how zoster-associated pain occurs and develops into PHN are elusive, making PHN difficult to predict. Uncovering the pathogenesis of zoster-associated pain (or HN) helps us to better understand the onset of PHN and supports developing more effective treatments. In this study, we successfully constructed a model for zoster-associated pain through varicella-zoster virus (VZV) infections of mouse footpads and pain behavior assessments. Next, we used the Kyoto Encyclopedia of Genes and Genomes (KEGG) and the Gene Ontology (GO) to analyze PHN rodent dorsal root ganglion (DRG) gene microarray data and found that calcium signal disorder might be involved in the onset of PHN. By using reverse transcription real-time fluorescent quantitative PCR (RT-qPCR) and Western blotting, we confirmed that VZV infection could significantly upregulate the expression of T-type calcium channel Cav3.2 in DRG and spinal dorsal horn (SDH). Intrathecal administration of Cav3.2 blocker (2R/S)-6-prenylnaringenin (6-PNG) relieved mechanical and thermal hyperalgesia induced by VZV. Taken together, our data indicated that VZV might participate in the occurrence and development of HN by upregulating the expression of Cav3.2 in DRG and SDH. These findings will help to reveal the underlying mechanisms on long-lasting pain and PHN formation, providing a new insight that Cav3.2 can be the promising drug target for remitting PHN.

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“…The gplots R package was used to construct the heatmaps (http://cran.r-project.org/web/packages/gplots/index.html), and the Draw Venn Diagram online tool was used to generate the Venn diagram (http://bioinformatics.psb.ugent.be/webtools/Venn/). 46 Functional classification of DEGs between groups was performed using the DAVID 6.8 (https://david.ncifcrf.gov/) 47 and KOBAS 3.0 (http://kobas.cbi.pku.edu.cn/kobas3) 48,49 online database. The sequencing data set supporting the results of this article has been submitted to the NCBI Gene Expression Omnibus (GEO) database, and the accession number is GSE208282.…”

Section: Methodsmentioning

confidence: 99%

HSV‐1 infection‐induced herpetic neuralgia involves a CCL5/CCR5‐mediated inflammation mechanism

Yang

et al. 2023

Journal of Medical Virology

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Herpetic-related neuralgia (HN) caused by varicella-zoster virus (VZV) infection is one of the most typical and common neuropathic pain in the clinic. However, the potential mechanisms and therapeutic approaches for the prevention and treatment of HN are still unclear. This study aims to provide a comprehensive understanding of the molecular mechanisms and potential therapeutic targets of HN. We used an HSV-1 infection-induced HN mouse model and screened the differentially expressed genes (DEGs) in the DRG and spinal cord using an RNAseq technique. Moreover, bioinformatics methods were used to figure out the signaling pathways and expression regulation patterns of the DEGs enriched.In addition, quantitative real-time RT-PCR and western blot were carried out to further confirm the expression of DEGs. HSV-1 inoculation in mice resulted in mechanical allodynia, thermal hyperalgesia, and cold allodynia, following the infection of HSV-1 in both DRG and spinal cord. Besides, HSV-1 inoculation induced an up-regulation of ATF3, CGRP, and GAL in DRG and activation of astrocytes and microglia in the spinal cord. Moreover, 639 genes were upregulated, 249 genes were downregulated in DRG, whereas 534 genes were upregulated and 12 genes were downregulated in the spinal cord of mice 7 days after HSV-1 inoculation. GO and KEGG enrichment analysis suggested that immune responses and cytokine-cytokine receptor interaction are involved in DRG and spinal cord neurons in mice after HSV-1 infection. In addition, CCL5 and its receptor CCR5 were significantly upregulated in DRG and spinal cord upon HSV-1 infection in mice. And blockade of CCR5 exhibited a significant analgesic effect and suppressed the upregulation of inflammatory cytokines in DRG and spinal cord induced by HSV-1 infection in mice. HSV-1 infection-induced allodynia and hyperalgesia in mice through dysregulation of immune response and cytokine-cytokine receptor interaction mechanism. Blockade of CCR5 alleviated allodynia and hyperalgesia probably through the suppression of

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Transcriptome Analysis Reveals the Role of Cellular Calcium Disorder in Varicella Zoster Virus-Induced Post-Herpetic Neuralgia

Cited by 18 publications

References 59 publications

Unraveling the immune signature of herpes zoster: Insights into pathophysiology and the HLA risk profile

Unraveling the immune signature of herpes zoster: Insights into pathophysiology and the HLA risk profile

Change in Cav3.2 T-Type Calcium Channel Induced by Varicella-Zoster Virus Participates in the Maintenance of Herpetic Neuralgia

HSV‐1 infection‐induced herpetic neuralgia involves a CCL5/CCR5‐mediated inflammation mechanism

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