{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,22]],"date-time":"2026-09-22T14:07:32Z","timestamp":1790086052386,"version":"4.0.1"},"reference-count":30,"publisher":"Wiley","issue":"9","license":[{"start":{"date-parts":[[2026,9,1]],"date-time":"2026-09-01T00:00:00Z","timestamp":1788220800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,9,1]],"date-time":"2026-09-01T00:00:00Z","timestamp":1788220800000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100001691","name":"Japan Society for the Promotion of Science","doi-asserted-by":"publisher","award":["24K10975"],"award-info":[{"award-number":["24K10975"]}],"id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Journal of Medical Virology"],"published-print":{"date-parts":[[2026,9]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>Hemophagocytic lymphohistiocytosis (HLH) is a severe, rapidly progressive disease. While viral infection is considered a common etiology of pediatric HLH, specific causative viruses other than the Epstein\u2010Barr virus (EBV) have been rarely identified. This study utilized metagenomic next\u2010generation sequencing (NGS) to identify potential causative pathogens in plasma samples from 17 pediatric patients with suspected HLH. Additionally, one case each of confirmed EBV\u2010 and cytomegalovirus (CMV)\u2010associated HLH was analyzed for methodological validation. Plasma cell\u2010free RNA (cfRNA) profiling was performed using NGS data to assess the host transcriptome response. Significant viral reads of human herpesvirus\u20106B, human herpesvirus\u20107, and Hubei reo\u2010like virus (HRLV) 14 were detected using metagenomic NGS in one patient each. Plasma cfRNA profiles from five patients with viral infection (including EBV and CMV) were compared to those of 14 patients without viral infection. By comparing the two patient groups, 1053 differentially expressed genes were identified. The gene ontology (GO) term of \u201cadaptive immune response\u201d (GO: 0002250) was significantly enriched among upregulated genes in the virus\u2010positive group. Furthermore, an isolated cluster consisting specifically of mitochondrial RNAs, was identified in the upregulated genes of the virus\u2010positive group. Using metagenomic NGS, several candidate viral pathogens were identified in patients with suspected infection\u2010related HLH. The viral genome of HRLV 14, previously undetected in human clinical samples, was identified in one patient. The results from plasma cfRNA profiling suggest that mitochondrial RNAs may reflect the underlying pathogenesis of virus\u2010associated HLH and have potential utility as disease biomarkers.<\/jats:p>","DOI":"10.1002\/jmv.71122","type":"journal-article","created":{"date-parts":[[2026,9,1]],"date-time":"2026-09-01T10:16:42Z","timestamp":1788257802000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Comprehensive Viral Detection and Profiling of Plasma Cell\u2010Free RNA in Patients With Suspected Hemophagocytic Lymphohistiocytosis"],"prefix":"10.1002","volume":"98","author":[{"ORCID":"https:\/\/orcid.org\/0009-0003-8290-5005","authenticated-orcid":false,"given":"Yuto","family":"Fukuda","sequence":"first","affiliation":[{"name":"Department of Pediatrics Nagoya University Graduate School of Medicine Nagoya 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