{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,23]],"date-time":"2026-09-23T06:12:52Z","timestamp":1790143972817,"version":"4.0.1"},"reference-count":36,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,9,23]],"date-time":"2026-09-23T00:00:00Z","timestamp":1790121600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Cell. Infect. Microbiol."],"abstract":"<jats:p>Herpes zoster (HZ) results from reactivation of latent varicella-zoster virus (VZV), and postherpetic neuralgia (PHN) is a major chronic pain complication. We performed parallel analyses of two independent public blood transcriptomic cohorts: GSE242252 (n=80; HZ onset, 1-year recovery, and controls) and PRJNA1142765 (n=23; 15 HZ and 8 PHN). Because the cohorts differed in platform, library preparation, design, and sampling structure, expression matrices were not merged; cross-cohort interpretation was restricted to within-cohort results and pathway-level directional concordance. HZ onset showed strong type I interferon (IFN)-dominated activation (HALLMARK_INTERFERON_ALPHA_RESPONSE, NES\u00a0=\u00a02.21, adjusted p=4.4x10-10), with recovery-associated attenuation of the sample-level IFN score (onset vs. recovery, p=0.005). In the smaller PHN cohort, only two genes met the strict differential-expression threshold, but Hallmark GSEA showed positive IFN-alpha and IFN-gamma enrichment. Ranking-sensitivity analysis confirmed IFN-alpha and IFN-gamma as the top two positively enriched Hallmark pathways using either log2 fold change or the DESeq2 Wald statistic, with leading-edge Jaccard similarities of 0.848 and 0.897, respectively. Exact patient-label permutation of the sample-level IFN score was not significant (two-sided p=0.297), although the PHN-minus-HZ direction remained positive in all 23 leave-one-out iterations. The new biological information is therefore an asymmetry of evidence: acute HZ IFN activation and recovery-associated attenuation are strongly supported, whereas the PHN-associated IFN pattern is stable at the pathway-ranking level but statistically uncertain at the patient level. Accordingly, the prior interpretation of persistent IFN activation in PHN is narrowed rather than reinforced. A structured external-replication search did not identify a suitable independent public human blood\/PBMC transcriptomic cohort containing PHN samples; external evidence was therefore treated as literature-based concordance and supportive context rather than validation. Restricted computational prioritization highlighted IFN-related and CCL5\/CCR5-associated axes for future study.<\/jats:p>","DOI":"10.3389\/fcimb.2026.1926554","type":"journal-article","created":{"date-parts":[[2026,9,23]],"date-time":"2026-09-23T05:50:15Z","timestamp":1790142615000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Blood transcriptomic immune signatures in herpes zoster and postherpetic neuralgia: parallel cohort analyses of IFN-related pathway patterns"],"prefix":"10.3389","volume":"16","author":[{"given":"Huiying","family":"Zhang","sequence":"first","affiliation":[{"name":"Department of Pain Medicine, Shaoxing People\u2019s Hospital","place":["Shaoxing, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yidong","family":"Zhu","sequence":"additional","affiliation":[{"name":"Hangzhou Sun Taihe Traditional Chinese Medicine and Pharmacy","place":["Hangzhou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Weijie","family":"Shao","sequence":"additional","affiliation":[{"name":"Hangzhou Fuyang Hospital of TCM Orthopedics and Traumatology","place":["Hangzhou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kai","family":"Xu","sequence":"additional","affiliation":[{"name":"The Second Affiliated Hospital of Zhejiang Chinese Medical University","place":["Hangzhou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,9,23]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"220","DOI":"10.1186\/s13059-017-1349-1","article-title":"xCell: digitally portraying the tissue cellular heterogeneity landscape","volume":"18","author":"Aran","year":"2017","journal-title":"Genome Biol."},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.1093\/bioadv\/vbac016","article-title":"decoupleR: ensemble of computational methods to infer biological activities from omics data","volume":"2","author":"Badia-I-Mompel","year":"2022","journal-title":"Bioinf. 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