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

D. Donati, N. Akhyani, A. Fogdell-Hahn, C. Cermelli, R. Cassiani-Ingoni, Alexander Vortmeyer, J. D. Heiss, P. Cogen, W. D. Gaillard, S. Sato, W. H. Theodore, S. Jacobson

Research output: Contribution to journalArticle

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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.

Original languageEnglish (US)
Pages (from-to)1405-1411
Number of pages7
JournalNeurology
Volume61
Issue number10
DOIs
StatePublished - Nov 25 2003
Externally publishedYes

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Human Herpesvirus 6
Temporal Lobe Epilepsy
Brain
Astrocytes
Glial Fibrillary Acidic Protein
Real-Time Polymerase Chain Reaction
Epilepsy
Exanthema Subitum
Western Blotting
Immunohistochemistry
Herpesviridae Infections
Herpesviridae
Central Nervous System Diseases
DNA

ASJC Scopus subject areas

  • Clinical Neurology

Cite this

Donati, D., Akhyani, N., Fogdell-Hahn, A., Cermelli, C., Cassiani-Ingoni, R., Vortmeyer, A., ... Jacobson, S. (2003). Detection of human herpesvirus-6 in mesial temporal lobe epilepsy surgical brain resections. Neurology, 61(10), 1405-1411. https://doi.org/10.1212/01.WNL.0000094357.10782.F9

Detection of human herpesvirus-6 in mesial temporal lobe epilepsy surgical brain resections. / Donati, D.; Akhyani, N.; Fogdell-Hahn, A.; Cermelli, C.; Cassiani-Ingoni, R.; Vortmeyer, Alexander; Heiss, J. D.; Cogen, P.; Gaillard, W. D.; Sato, S.; Theodore, W. H.; Jacobson, S.

In: Neurology, Vol. 61, No. 10, 25.11.2003, p. 1405-1411.

Research output: Contribution to journalArticle

Donati, D, Akhyani, N, Fogdell-Hahn, A, Cermelli, C, Cassiani-Ingoni, R, Vortmeyer, A, Heiss, JD, Cogen, P, Gaillard, WD, Sato, S, Theodore, WH & Jacobson, S 2003, 'Detection of human herpesvirus-6 in mesial temporal lobe epilepsy surgical brain resections', Neurology, vol. 61, no. 10, pp. 1405-1411. https://doi.org/10.1212/01.WNL.0000094357.10782.F9
Donati, D. ; Akhyani, N. ; Fogdell-Hahn, A. ; Cermelli, C. ; Cassiani-Ingoni, R. ; Vortmeyer, Alexander ; Heiss, J. D. ; Cogen, P. ; Gaillard, W. D. ; Sato, S. ; Theodore, W. H. ; Jacobson, S. / Detection of human herpesvirus-6 in mesial temporal lobe epilepsy surgical brain resections. In: Neurology. 2003 ; Vol. 61, No. 10. pp. 1405-1411.
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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.",
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AU - Donati, D.

AU - Akhyani, N.

AU - Fogdell-Hahn, A.

AU - Cermelli, C.

AU - Cassiani-Ingoni, R.

AU - Vortmeyer, Alexander

AU - Heiss, J. D.

AU - Cogen, P.

AU - Gaillard, W. D.

AU - Sato, S.

AU - Theodore, W. H.

AU - Jacobson, S.

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