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

INTRODUCTION

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.

OBJECTIVE

In this study, we investigated global changes in phosphorylation levels in HZ patients with postherpetic neuralgia (PHN) compared to healthy controls.

METHODS

Using publicly available datasets, we found that the serine/threonine protein kinase and phosphatase pathways are significantly regulated by VZV infection, suggesting that VZV infection might globally alter the phosphorome of the host. To test this hypothesis, the phosphoproteomes of peripheral blood collected from HZ patients with PHN were profiled and differentially phosphorylated proteins were identified.

RESULTS

The enhanced phosphorylated proteins were involved in pathways including complement activation, coagulation cascades, and endoplasmic reticulum protein processing. Variations in the phosphorylation levels of several proteins were highly consistent with a previously published proteomic study, indicating the synergistic regulation of protein translation and post-translational modification.

CONCLUSION

Notably, kinase-substrate enrichment analysis identified CSNK2A1 and PRKACA as potential response kinases, whereas their transcription and protein levels were experimentally validated to be significantly altered after VZV infection, showing the same trend. Furthermore, Mendelian randomization (MR) analysis revealed that decreased expression of CSNK2A1 may lead to a higher risk of HZ, indicating a vital role of this kinase during anti-VZV infection. Collectively, our findings provide valuable insights into the molecular mechanisms underlying VZV infection and highlight potential therapeutic targets for further investigation.