Hippocampal Gene Expression in Mesial Temporal Lobe Epilepsy With Hippocampal Sclerosis: Assessment of Human Herpesvirus 6B DNA Status

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.