ArticleFrontiers in immunology2026
gE mutations and VZV genotypes jointly predict pain relief outcomes in herpes zoster: an integrative immunologic and modeling study.
Article in Frontiers in immunology, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
Introduction: Herpes zoster (HZ), caused by reactivation of varicella-zoster virus (VZV), is associated with significant pain burden and risk of postherpetic neuralgia (PHN). However, early prediction of pain outcomes remains limited due to insufficient integration of viral genotypic features and host immune responses. This study aimed to investigate the distribution of VZV genotypes, characterize glycoprotein E (gE) mutations, and evaluate their associations with immunological markers and pain outcomes in HZ patients. Methods: A total of 52 HZ outpatients from Chongqing were enrolled, and 46 samples were successfully sequenced. VZV genotyping was performed using SNP analysis of the ORF22 region, and gE gene mutations were analyzed by PCR and sequencing. Clinical data and immunological indicators, including gE antigen, gE antibody (gEAb), immunoglobulins, complement levels, and CD4+ T cells, were collected. A predictive model for pain outcomes was developed using L1-regularized regression with cross-validation. Results: Clade 2 (J-type) was the predominant genotype (76.1%), followed by Clade 3, Clade 4, and minor proportions of Clade 1 and 5. Frequent missense mutations were observed in the gE gene, particularly a T→I substitution at positions 250-291 in 67.4% of cases. The average numbers of mutations and deletions were 13.46 ± 8.07 and 5.00 ± 3.71, respectively. Immunological analysis showed detectable gE antigen and antibody levels, elevated IgG, and normal complement and CD4+ T cell levels, indicating active humoral immunity. The predictive model demonstrated good performance for identifying poor pain relief (AUC = 0.87; PR-AUC = 0.74), with gE-related variables consistently contributing to prediction. Discussion: This study demonstrates the predominance of Clade 2 VZV and identifies characteristic gE mutation patterns in HZ patients from Chongqing. The findings highlight the role of gE-related immune responses in disease progression and pain outcomes. gE may serve as a potential biomarker for clinical stratification and prediction of prolonged pain, providing insights into immunopathogenesis and personalized management of HZ.
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