HHV-7 in adults with drug-resistant epilepsy: a pathological role in hippocampal sclerosis?

J Clin Virol. 2014 Nov;61(3):387-92. doi: 10.1016/j.jcv.2014.08.017. Epub 2014 Aug 29.

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.

Objectives: 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.

Study design: 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.

Results and 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.

Keywords: Hippocampal sclerosis; Human herpesvirus-7; Transforming growth factor-beta.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Brain Diseases / complications
  • Brain Diseases / diagnosis*
  • Cytokines / analysis
  • Cytokines / genetics
  • DNA, Viral / analysis
  • DNA, Viral / genetics
  • Epilepsy / etiology*
  • Herpesvirus 7, Human / isolation & purification*
  • Hippocampus / pathology*
  • Humans
  • Immunohistochemistry
  • Male
  • Middle Aged
  • Polymerase Chain Reaction
  • Real-Time Polymerase Chain Reaction
  • Roseolovirus Infections / complications
  • Roseolovirus Infections / diagnosis*
  • Sclerosis / complications*
  • Sclerosis / etiology*
  • Viral Proteins / analysis
  • Young Adult

Substances

  • Cytokines
  • DNA, Viral
  • Viral Proteins