Detection of human herpesvirus-6 in mesial temporal lobe epilepsy surgical brain resections

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Abstract
Background: Human herpesvirus-6 (HHV-6), a ubiquitous β-herpesvirus, is the causative agent of roseola infantum and has been associated with a number of neurologic disorders including seizures, encephalitis/meningitis, and multiple sclerosis. Although the role of HHV-6 in human CNS disease remains to be fully defined, a number of studies have suggested that the CNS can be a site for persistent HHV-6 infection. Objective: To characterize the extent and distribution of HHV-6 in human glial cells from surgical brain resections of patients with mesial temporal lobe epilepsy (MTLE). Method: Brain samples from eight patients with MTLE and seven patients with neocortical epilepsy (NE) undergoing surgical resection were quantitatively analyzed for the presence of HHV-6 DNA using a virus-specific real-time PCR assay. HHV-6 expression was also characterized by western blot analysis and in situ immunohistochemistry (IHC). In addition, HHV-6-reactive cells were analyzed for expression of glial fibrillary acidic protein (GFAP) by double immunofluorescence. Results: DNA obtained from four of eight patients with MTLE had significantly elevated levels of HHV-6 as quantified by real-time PCR. HHV-6 was not amplified in any of the seven patients with NE undergoing surgery. The highest levels of HHV-6 were demonstrated in hippocampal sections (up to 23,079 copies/106 cells) and subtyped as HHV-6B. Expression of HHV-6 was confirmed by western blot analysis and IHC. HHV-6 was co-localized to GFAP-positive cells that morphologically appeared to be astrocytes. Conclusions: HHV-6B is present in brain specimens from a subset of patients with MTLE and localized to astrocytes in the absence of inflammation. The amplification of HHV-6 from hippocampal and temporal lobe astrocytes of MTLE warrants further investigation into the possible role of HHV-6 in the development of MTLE.