Jin-Mei Li1, Cheng Huang1, Bo Yan1, Wei Wang1, Qiao Zhou2, Josemir W Sander3, Dong Zhou4. 1. Department of Neurology, West China Hospital of Sichuan University, Chengdu, China. 2. Department of Pathology, West China Hospital of Sichuan University, Chengdu, China. 3. NIHR University College London Hospital Biomedical Research Centre, UCL Institute of Neurology, China. 4. Department of Neurology, West China Hospital of Sichuan University, Chengdu, China. Electronic address: zhoudong66@yahoo.de.
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.
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.