Detection of human herpesvirus-6 in mesial temporal lobe epilepsy surgical brain resections.
BACKGROUND
Human herpesvirus-6 (HHV-6), a ubiquitous beta-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).


METHODS
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/10(6) 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.
Donati
D
D
Neuroimmunology Branch, National Institute of Neurological Disorders and Stroke, NIH, Bethesda, MD 20892, USA.
Akhyani
N
N
Fogdell-Hahn
A
A
Cermelli
C
C
Cassiani-Ingoni
R
R
Vortmeyer
A
A
Heiss
J D
JD
Cogen
P
P
Gaillard
W D
WD
Sato
S
S
Theodore
W H
WH
Jacobson
S
S
D000293:Adolescent; D000328:Adult; D000956:Antigens, Viral / Q000032:analysis / Q000276:immunology; D015153:Blotting, Western; D001921:Brain / Q000601:surgery / Q000821:virology*; D002648:Child; D004279:DNA, Viral / Q000032:analysis; D004268:DNA-Binding Proteins / Q000032:analysis; D004833:Epilepsy, Temporal Lobe / Q000601:surgery / Q000821:virology*; D005260:Female; D005904:Glial Fibrillary Acidic Protein / Q000032:analysis / Q000276:immunology; D015654:Herpesvirus 6, Human / Q000235:genetics / Q000302:isolation & purification*; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D009457:Neuroglia / Q000737:chemistry / Q000821:virology; D013702:Temporal Lobe / Q000821:virology; D014764:Viral Proteins / Q000032:analysis
D000956:Antigens, Viral; D004279:DNA, Viral; D004268:DNA-Binding Proteins; D005904:Glial Fibrillary Acidic Protein; D014764:Viral Proteins; C081690:p41 protein, Human herpesvirus 6