Dataset Information

Kinases Responding to Herpes Zoster Virus Infection Unveiled by Phosphoromics Profiling

ABSTRACT: Reactivation of varicella-zoster virus (VZV) causes herpes zoster (HZ) in humanity and elicits VZV-specific immune response. Yet the impact of VZV on host proteins post-translational modifications (PTMs) remains largely untapped. In this study, we investigated the global changes of phosphorylation levels in HZ patients compared with healthy control. Through publicly available datasets, we found that the serine/threonine protein kinase and phosphatase pathways were significantly regulated by VZV infection, suggesting that VZV infection might globally alter the phosphorome of host. To test this hypothesis, the phosphoproteomes of peripheral blood collected from HZ patients were profiled, differentially phosphorylated proteins after VZV infection were identified. The enhanced phosphorylated proteins were involved in pathways including complement activation, coagulation cascades, and endoplasmic reticulum protein processing. Variations in phosphorylation level of several proteins are highly corresponding to a previous published proteomic study, indicating synergistic regulation of the protein translation and post-translational modification. Notably, kinase-substrate enrichment analysis identified CSNK2A1 and PRKACA as potential response kinase, while their transcription and protein levels were experimentally validated to be significantly altered after VZV infection and showed the same trend. Furthermore, Mendelian randomization (MR) analysis revealed decreased expression of CSNK2A1 may lead to higher risk of HZ, manifesting vital role of this kinase during anti-VZV infection. Together, our findings provide valuable insights into the molecular mechanisms underlying VZV infection and highlight potential therapeutic targets for further investigation.

INSTRUMENT(S):

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Blood

DISEASE(S): Herpes Zoster

SUBMITTER: Wang xinpei

LAB HEAD: Hongxiang Xu

PROVIDER: PXD058933 | Pride | 2026-02-09

REPOSITORIES: Pride

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Kinases Associated with Herpes Zoster Virus Infection Unveiled by Phosphoromics Profiling.

Xia Juan J Xu Hongxiang H Wang Xinpei X Mei Yang Y Zhang Tianyu T Dong Yiping Y Li Wei W Deng Zhong-Liang ZL

Infection and drug resistance 20250531

<h4>Introduction</h4>Reactivation of varicella-zoster virus (VZV) causes herpes zoster (HZ) in humans and elicits a VZV-specific immune response. However, the effect of VZV on host protein post-translational modifications (PTMs) remains largely unknown.<h4>Objective</h4>In this study, we investigated global changes in phosphorylation levels in HZ patients with postherpetic neuralgia (PHN) compared to healthy controls.<h4>Methods</h4>Using publicly available datasets, we found that the serine/thr ...[more]

PMID: 40469476

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Project description:Varicella-zoster virus (VZV) encephalitis and meningitis are potential central nervous system (CNS) complications following primary VZV infection or reactivation. With innate immune signalling, and more specifically type I interferon (IFN) signalling, being an important first line cellular defence mechanism against VZV infection, we here investigated the triggering of innate immune responses in a human CNS-like environment. For this, we established and characterised a 5-month matured hiPSC-derived neurospheroid (NSPH) model containing TuJ1+ MAP2+ NeuN+ neurons and GFAP+ S100b+ AQP4+ CD49f+ astrocytes. Immune competence of these NSPHs was demonstrated by secretion of IL-6 and CXCL10 following stimulation with a cocktail of pro-inflammatory stimuli. Subsequently, NSPHs were infected with reporter strains of VZV (eGFP-ORF23 VZV) and Sendai virus (eGFP SeV). Live cell and immunocytochemical analyses demonstrated VZV infection within NSPHs, while SeV infection was limited to the outer NSPH border. Next, a transcript-level immune profiling was performed using NanoString technology to explore innate immune signatures of virus-infected NSPHs. While SeV-infected NSPHs displayed a clear Type I IFN response, in VZV-infected NSPHs no Type I IFN response was activated. Even more, in the latter a strong suppression of genes related to IFN signalling and antigen presentation was noted. Validating these opposite immune signatures in VZV- and SeV-infected NSPHs, cytokine profiling of NSPH supernatant revealed increased secretion of IL6 and CXCL10 by SeV-infected NSPHs, but not by VZV-infected NSPHs. Similarly, immunocytochemical analysis demonstrated upregulation of type I IFN activated anti-viral proteins Mx1, IFIT2 and ISG15 in SeV-infected NSPHs, but not in VZV-infected NSPHs. Furthermore, CD74, a key part of the MHC class II antigen presentation pathway was found to be suppressed in VZV-infected NSPHs. Finally, even though VZV-infection seems to be immunologically ignored in NSPHs, its presence does result in the formation of stress granules throughout the entire NSPH. Concluding, in this study we demonstrate that 5-month matured hiPSC-derived NSPHs display functional innate immune reactivity towards SeV infection, as well as their capability to recapitulate the strong immune evasive behaviour of VZV. Subsequently, this NSPH model has the potential to study viral neuro-immune responses and evasion strategies in a human CNS-like environment.

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