title: HHV-7 in adults with drug-resistant epilepsy: a pathological role in hippocampal sclerosis?
abstract: BACKGROUND
  Human herpesvirus-7 (HHV-7) is a β-herpesvirus associated with febrile seizures. No association between HHV-7 and epilepsy has been confirmed.
  
  
  OBJECTIVE
  The aim of this study was to investigate the presence of HHV-7 protein (KR4) in brain tissue from patients with drug-resistant epilepsy and to determine whether inflammatory molecules are activated in the presence of HHV-7 infection.
  
  
  METHODS
  We used immunohistochemistry (IHC) to detect HHV-7 protein KR4 in samples from 305 patients with drug-resistant epilepsy. Liquid nitrogen-preserved hippocampal sclerosis (HS) samples from 63 of these patients were available, and we used nested polymerase chain reaction (PCR) to detect HHV-7 DNA. Inflammatory molecules including tumor necrosis factor-alpha (TNF-α), transforming growth factor-beta (TGF-β), interleukin-1 (IL-1) and interleukin-6 (IL-6) were identified by real-time PCR (rt-PCR) and IHC.
  
  
  CONCLUSIONS
  The study sample included 201 male subjects. The mean age was 23.9, SD 6.2 years (range 15-45). HS was the pathology in 69 samples (23%). The HHV-7 protein was detected in 27 (9%) of the 305 samples and in none of the 42 controls. The factors associated with HHV-7 infection were HS (11/69), glial scar (8/58), arachnoid cyst (2/21), focal cortical dysplasia (2/31) and vascular malformation (4/52). HHV-7 antigen was distributed mainly in the cytoplasm of astrocyte and oligodendrocyte in HS samples. HHV-7 DNA was detected in 20 of the 63 nitrogen preserved HS samples. The expression of TGF-β was up-regulated in samples that were positive for the HHV-7 protein and was mainly detected in neurons. This finding suggests a possible association between HHV-7 positivity, activation of TGF-β and drug-resistant epilepsy, especially HS, but these data need to be replicated.
authors.affiliation: Department of Neurology, West China Hospital of Sichuan University, Chengdu, China.
authors.forename: Jin-Mei
authors.initials: JM
authors.lastname: Li
authors.affiliation: Department of Neurology, West China Hospital of Sichuan University, Chengdu, China.
authors.forename: Cheng
authors.initials: C
authors.lastname: Huang
authors.affiliation: Department of Neurology, West China Hospital of Sichuan University, Chengdu, China.
authors.forename: Bo
authors.initials: B
authors.lastname: Yan
authors.affiliation: Department of Neurology, West China Hospital of Sichuan University, Chengdu, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Wang
authors.affiliation: Department of Pathology, West China Hospital of Sichuan University, Chengdu, China.
authors.forename: Qiao
authors.initials: Q
authors.lastname: Zhou
authors.affiliation: NIHR University College London Hospital Biomedical Research Centre, UCL Institute of Neurology, China.
authors.forename: Josemir W
authors.initials: JW
authors.lastname: Sander
authors.affiliation: Department of Neurology, West China Hospital of Sichuan University, Chengdu, China. Electronic address: zhoudong66@yahoo.de.
authors.forename: Dong
authors.initials: D
authors.lastname: Zhou
mesh_terms: D000293:Adolescent; D000328:Adult; D001927:Brain Diseases / Q000150:complications / Q000175:diagnosis*; D016207:Cytokines / Q000032:analysis / Q000235:genetics; D004279:DNA, Viral / Q000032:analysis / Q000235:genetics; D004827:Epilepsy / Q000209:etiology*; D016199:Herpesvirus 7, Human / Q000302:isolation & purification*; D006624:Hippocampus / Q000473:pathology*; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D016133:Polymerase Chain Reaction; D060888:Real-Time Polymerase Chain Reaction; D019349:Roseolovirus Infections / Q000150:complications / Q000175:diagnosis*; D012598:Sclerosis / Q000150:complications* / Q000209:etiology*; D014764:Viral Proteins / Q000032:analysis; D055815:Young Adult
chemical_list: D016207:Cytokines; D004279:DNA, Viral; D014764:Viral Proteins
keywords: Hippocampal sclerosis; Human herpesvirus-7; Transforming growth factor-beta