ABSTRACT Mesial temporal lobe epilepsy with hippocampal sclerosis (MTLE‐HS) is an intractable form of epilepsy involving the hippocampus, and temporal lobectomy remains an effective treatment. Human herpesvirus 6B (HHV‐6B) establishes latency in the hippocampus and may contribute to MTLE‐HS pathogenesis by altering host gene expression; however, transcriptomic data from healthy controls remain limited. This study investigated the role of HHV‐6B to MTLE‐HS pathogenesis by analyzing gene expression in resected hippocampal tissues. Samples were collected from 12 to 43 HHV‐6 DNA‐positive and ‐negative patients, respectively, and three controls. RNA sequencing was performed on eight representative samples, followed by RT‐qPCR validation of nine selected genes in 58 samples. RNA sequencing identified 600 differentially expressed genes (210 upregulated, 390 downregulated) between HHV‐6B‐positive MTLE‐HS and controls. Pathway enrichment analysis revealed involvement of synaptic signaling and inflammatory responses, with prostaglandin biosynthesis specifically upregulated in HHV‐6B‐positive tissues. Two genes were significantly upregulated in HHV‐6B‐positive compared with HHV‐6B‐negative samples. RT‐qPCR confirmed elevated cholesterol 25‐hydroxylase and interleukin 1 beta expression in HHV‐6 DNA‐positive samples (both p = 0.031). These findings suggest that HHV‐6B may contribute to MTLE‐HS pathogenesis by modulating the expression of host inflammatory genes, supporting a role for neuroinflammation and the potential benefits of anti‐inflammatory therapies.
Kawamura et al. (Sun,) studied this question.
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