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HSV-1 reactivation results in post-herpetic neuralgia by upregulating Prmt6 and inhibiting cGAS-STING.

ABSTRACT: Chronic varicella zoster virus (VZV) infection induced neuroinflammatory condition is the critical pathology of post-herpetic neuralgia (PHN). The immune escape mechanism of VZV remains elusive. As to mice have no VZV infection receptor, herpes simplex virus type 1 (HSV-1) infection is a well established PHN mice model. Transcriptional expression analysis identified that the protein arginine methyltransferases 6 (Prmt6) was upregulated upon HSV-1 infection, which was further confirmed by immunofluorescence staining in spinal dorsal horn. Prmt6 deficiency decreased HSV-1-induced neuroinflammation and PHN by enhancing antiviral innate immunity and decreasing HSV-1 load in vivo and in vitro. Overexpression of Prmt6 in microglia dampened antiviral innate immunity and increased HSV-1 load. Mechanistically, Prmt6 methylated and inactivated STING, resulting in reduced phosphorylation of TANK binding kinase-1 (TBK1) and interferon regulatory factor 3 (IRF3), diminished production of type I interferon (IFN-I) and antiviral innate immunity. Furthermore, intrathecal or intraperitoneal administration of the Prmt6 inhibitor EPZ020411 decreased HSV-1-induced neuroinflammation and PHN by enhancing antiviral innate immunity and decreasing HSV-1 load. Our findings revealed that HSV-1 escapes antiviral innate immunity and results in PHN by upregulating Prmt6 expression and inhibiting the cGAS-STING pathway, providing novel insights and a potential therapeutic target for PHN.

SUBMITTER: Kong E

PROVIDER: S-EPMC11224619 | biostudies-literature | 2024 Jul

REPOSITORIES: biostudies-literature

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HSV-1 reactivation results in post-herpetic neuralgia by upregulating Prmt6 and inhibiting cGAS-STING.

Kong Erliang E Hua Tong T Li Jian J Li Yongchang Y Yang Mei M Ding Ruifeng R Wang Haowei H Wei Huawei H Feng Xudong X Han Chaofeng C Yuan Hongbin H

Brain : a journal of neurology 20240701 7

Chronic varicella zoster virus (VZV) infection induced neuroinflammatory condition is the critical pathology of post-herpetic neuralgia (PHN). The immune escape mechanism of VZV remains elusive. As to mice have no VZV infection receptor, herpes simplex virus type 1 (HSV-1) infection is a well established PHN mice model. Transcriptional expression analysis identified that the protein arginine methyltransferases 6 (Prmt6) was upregulated upon HSV-1 infection, which was further confirmed by immunof ...[more]

PMID: 38366606

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Project description:Background and objectivesThere are limited data examining the real-world use of gabapentin and pregabalin for the treatment of post-herpetic neuralgia (PHN). This study examines dosing patterns, therapy outcomes, healthcare utilization and costs of patients with PHN who initiate treatment with gabapentin or pregabalin.MethodsThis was a retrospective administrative claims data analysis from July 2005 to February 2010. Patients with PHN initiating gabapentin or pregabalin (index therapy) from January 2006 to February 2009 were identified and were observed for 12 months after index therapy initiation. Outcomes were mean daily dosages of the index therapy, attainment of minimally effective dosages of gabapentin (≥ 1,800 mg/day) or pregabalin (≥ 150 and ≥ 300 mg/day) persistence, discontinuation, index therapy switching, addition of neuropathic pain medications to index therapy, and healthcare resource use and costs.Results1,645 patients were identified. The mean daily dosage was 826 mg for gabapentin and 187 mg for pregabalin. Only 52.6 % of patients initiating gabapentin and 56.9 % initiating pregabalin obtained a refill during the post-index period. Approximately 14 % of patients treated with gabapentin reached the target dosage (1,800 mg/day). For pregabalin, 87 % reached ≥ 150 mg/day and 27 % reached ≥ 300 mg/day. On average, patients took 10 weeks to reach 1,800 mg/day gabapentin, and 5.0 and 9.2 weeks to reach ≥ 150 mg/day and ≥ 300 mg/day pregabalin, respectively. Approximately one-third of patients in both index therapy cohorts added a pain medication; more than half added opioids. The percentage of patients switching from either drug (57 %) or adding a therapy (34 %) were similar between index therapy cohorts; opioids were the most common therapy patients switched to or added.ConclusionIt appears that gabapentin and pregabalin are not used effectively to treat PHN. Suboptimal dosing and discontinuation may be associated with supplementary use of other analgesics, especially opioids.

Project description:BackgroundThere are still controversies between the curative effect of acupuncture combined with cupping therapy and western medicine for post-herpetic neuralgia (PHN). Our meta-analysis fully incorporates the research of acupuncture combined with cupping therapy versus Western medicine for PHN, aiming to explore the difference in the efficacy of the 2 therapies, so as to provide guidance for clinical treatment.MethodsWe searched PubMed, Embase, Cochrane Library, CNKI, Wanfang, CQVIP, CBM, from establishment of the database to September, 2020. Include studies that are clearly defined as PHN or herpes zoster, and exclude duplicate publications; studies with no full text, incomplete information, or inability to extract data; the definition of exposure is quite different from most literature; animal experiments.ResultsThe total effective rate (relative ratio [RR] = 1.21, 95% confidence interval [CI]: 1.12-1.31) and the rate of remarkable effect (RR = 1.46, 95% CI: 1.30-1.63) of acupuncture and moxibustion combined with cupping in the treatment of PHN were significantly higher than that of conventional western medicine. The visual analogue scale score of acupuncture and moxibustion combined with cupping for PHN was significantly lower than that of conventional western medicine treatment (WMD = -1.77, 95% CI [-2.79, -0.75]). In addition, acupuncture and moxibustion combined with cupping therapy significantly reduced the occurrence of PHN compared with conventional western medicine treatment after treatment of acute herpes zoster (RR = 0.30, 95% CI: 0.20-0.45). In order to explore the differences in the efficacy and preventive effects of different types of acupuncture and cupping therapy, we have further conducted a subgroup analysis.ConclusionThe effect of acupuncture and moxibustion combined with cupping in the treatment of PHN is significantly higher than that of conventional western medicine, and it can significantly prevent the occurrence of PHN. Chinese medicine should be used more widely in the treatment of PHN.

Dataset Information

HSV-1 reactivation results in post-herpetic neuralgia by upregulating Prmt6 and inhibiting cGAS-STING.

Publications

HSV-1 reactivation results in post-herpetic neuralgia by upregulating Prmt6 and inhibiting cGAS-STING.

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