title: Association of human herpesvirus-6B with mesial temporal lobe epilepsy.
abstract: BACKGROUND
  Human herpesvirus-6 (HHV-6) is a beta-herpesvirus with 90% seroprevalence that infects and establishes latency in the central nervous system. Two HHV-6 variants are known: HHV-6A and HHV-6B. Active infection or reactivation of HHV-6 in the brain is associated with neurological disorders, including epilepsy, encephalitis, and multiple sclerosis. In a preliminary study, we found HHV-6B DNA in resected brain tissue from patients with mesial temporal lobe epilepsy (MTLE) and have localized viral antigen to glial fibrillary acidic protein (GFAP)-positive glia in the same brain sections. We sought, first, to determine the extent of HHV-6 infection in brain material resected from MTLE and non-MTLE patients; and second, to establish in vitro primary astrocyte cultures from freshly resected brain material and determine expression of glutamate transporters.
  
  
  RESULTS
  HHV-6B infection in astrocytes and brain specimens was investigated in resected brain material from MTLE and non-MTLE patients using PCR and immunofluorescence. HHV-6B viral DNA was detected by TaqMan PCR in brain resections from 11 of 16 (69%) additional patients with MTLE and from zero of seven (0%) additional patients without MTLE. All brain regions that tested positive by HHV-6B variant-specific TaqMan PCR were positive for viral DNA by nested PCR. Primary astrocytes were isolated and cultured from seven epilepsy brain resections and astrocyte purity was defined by GFAP reactivity. HHV-6 gp116/54/64 antigen was detected in primary cultured GFAP-positive astrocytes from resected tissue that was HHV-6 DNA positive-the first demonstration of an ex vivo HHV-6-infected astrocyte culture isolated from HHV-6-positive brain material. Previous work has shown that MTLE is related to glutamate transporter dysfunction. We infected astrocyte cultures in vitro with HHV-6 and found a marked decrease in glutamate transporter EAAT-2 expression.
  
  
  CONCLUSIONS
  Overall, we have now detected HHV-6B in 15 of 24 patients with mesial temporal sclerosis/MTLE, in contrast to zero of 14 with other syndromes. Our results suggest a potential etiology and pathogenic mechanism for MTLE.
authors.affiliation: Viral Immunology Section, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, Maryland, United States of America.
authors.forename: Julie
authors.initials: J
authors.lastname: Fotheringham
authors.forename: Donatella
authors.initials: D
authors.lastname: Donati
authors.forename: Nahid
authors.initials: N
authors.lastname: Akhyani
authors.forename: Anna
authors.initials: A
authors.lastname: Fogdell-Hahn
authors.forename: Alexander
authors.initials: A
authors.lastname: Vortmeyer
authors.forename: John D
authors.initials: JD
authors.lastname: Heiss
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Williams
authors.forename: Steven
authors.initials: S
authors.lastname: Weinstein
authors.forename: Derek A
authors.initials: DA
authors.lastname: Bruce
authors.forename: William D
authors.initials: WD
authors.lastname: Gaillard
authors.forename: Susumu
authors.initials: S
authors.lastname: Sato
authors.forename: William H
authors.initials: WH
authors.lastname: Theodore
authors.forename: Steven
authors.initials: S
authors.lastname: Jacobson
mesh_terms: D000293:Adolescent; D000328:Adult; D001253:Astrocytes / Q000166:cytology / Q000821:virology; D001921:Brain / Q000473:pathology / Q000821:virology; D036022:Capsid Proteins / Q000235:genetics; D002478:Cells, Cultured; D002648:Child; D004279:DNA, Viral / Q000235:genetics; D004833:Epilepsy, Temporal Lobe / Q000473:pathology* / Q000821:virology*; D015967:Gene Expression Regulation, Viral; D015654:Herpesvirus 6, Human / Q000235:genetics* / Q000302:isolation & purification*; D006801:Humans; D007223:Infant; D008875:Middle Aged; D016133:Polymerase Chain Reaction; D012333:RNA, Messenger / Q000235:genetics; D019349:Roseolovirus Infections / Q000150:complications*; D014158:Transcription, Genetic
chemical_list: D036022:Capsid Proteins; D004279:DNA, Viral; D012333:RNA, Messenger