Hiroki Miura | Search PubMed

PubMed2026

A Patient-Derived iPSC-Based Model Reveals Neural Lineage-Specific Transcription of Endogenous HHV-6B.

BACKGROUND: Endogenous human herpesvirus 6 (eHHV-6), in which the entire viral genome is integrated into human chromosomes, is present in approximately 1% of the population and has been associated with various clinical conditions, including neurological disorders. However, its biological significance remains unclear due to the lack of appropriate experimental models. METHODS: We established a patient-derived induced pluripotent stem cell (iPSC)-based tissue culture model using lymphoblastoid cell lines from individuals with eHHV-6B. iPSCs retaining the integrated viral genome were generated and subsequently differentiated into neural stem cells (NSCs). Viral gene expression was evaluated by RT-qPCR under basal conditions and following chemical stimulation. RESULTS: The integrated HHV-6B genome was transcriptionally silent in iPSCs but exhibited spontaneous low-level expression of the immediate-early gene U90 and the late gene U100 in NSCs. Chemical stimulation further enhanced U90 expression, whereas induction of U100 did not reach statistical significance. These findings indicate preferential activation of early viral transcriptional programs in neural lineage cells. CONCLUSIONS: Neural lineage cells provide a permissive environment for expression of eHHV-6B transcripts. This patient-derived iPSC-based model provides a platform for investigating the biological significance of neural lineage-specific eHHV-6 transcripts and may facilitate interpretation of HHV-6 DNA detection in patients with eHHV-6 by enabling studies of cell type-dependent viral transcription.

endogenous HHV-6↗

PubMed2026

Comprehensive Viral Detection and Profiling of Plasma Cell-Free RNA in Patients With Suspected Hemophagocytic Lymphohistiocytosis.

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-Barr virus (EBV) have been rarely identified. This study utilized metagenomic next-generation sequencing (NGS) to identify potential causative pathogens in plasma samples from 17 pediatric patients with suspected HLH. Additionally, one case each of confirmed EBV- and cytomegalovirus (CMV)-associated HLH was analyzed for methodological validation. Plasma cell-free RNA (cfRNA) profiling was performed using NGS data to assess the host transcriptome response. Significant viral reads of human herpesvirus-6B, human herpesvirus-7, and Hubei reo-like 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 "adaptive immune response" (GO: 0002250) was significantly enriched among upregulated genes in the virus-positive group. Furthermore, an isolated cluster consisting specifically of mitochondrial RNAs, was identified in the upregulated genes of the virus-positive group. Using metagenomic NGS, several candidate viral pathogens were identified in patients with suspected infection-related 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-associated HLH and have potential utility as disease biomarkers.

Humans↗