Latent, Early or Late Human Herpes Virus-6B Expression in Adult Mesial Temporal Lobe Epilepsy: Association of Virus Life Cycle with Inflammatory Cytokines in Brain Tissue and Cerebral Spinal Fluid

Neuroscience. 2022 Nov 10;504:21-32. doi: 10.1016/j.neuroscience.2022.08.021. Epub 2022 Sep 5.

Abstract

Background: Human herpes virus-6B (HHV-6B) was suggested as an important etiologic factor of mesial temporal lobe epilepsy, while the mechanism is still unknown. Here, we aimed to analyze antigens representing latent, early and late HHV-6B infection and the association with inflammatory cytokines in brain tissue and cerebral spinal fluid (CSF) from MTLE patients with HHV-6B-positivity.

Methods: Nested polymerase chain reaction (nPCR), real-time PCR, immunohistochemistry (IHC) and suspension bead array for cytokines were performed.

Results: Nested polymerase chain reaction (nPCR) in brain tissue revealed HHV-6B DNA in 19 of 49 MTLE patients (39%) and 1 of 19 controls (5%) (P < 0.001), but not in CSF. ICH showed HHV-6B early antigen (P41) positivity in 3 patients (6%), late antigen (gp116/54/64) positivity in 5 patients (10%), latent antigen (U94) positivity in 8 patients (16%), and multiple antigen (early and late or/and latent) positivity in 9 patients (18%). None of these HHV-6B related proteins were found positive in control brain tissue. PCR revealed significant up-regulation of IL-1a, IL-2 and IL-7 mRNA levels in the brain tissue from MTLE patients expressing early antigens compared to those expressing late, latent, multiple antigens, negative antigens and the controls. Suspension bead array of the CSF confirmed significant up-regulation of IL-1a and IL-7 protein expression from MTLE patients expressing early antigens compared to the other groups.

Conclusions: Our finding suggests HHV-6B is a common etiologic agent of MTLE. Different virus life cycle may play an important modifying role in inflammatory biology that warrants further investigation. Though virus DNA is difficult detected in CSF, up-regulation of IL-1a and IL-7 in CSF indicates the two cytokines may be taken as indirect biomarker of HHV-6B infection.

Keywords: human herpes virus-6B; immunohistochemistry; inflammatory cytokines; mesial temporal lobe epilepsy; polymerase chain reaction.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Animals
  • Brain
  • Cytokines / genetics
  • Epilepsy, Temporal Lobe*
  • Herpesvirus 6, Human* / genetics
  • Humans
  • Interleukin-7 / genetics
  • Life Cycle Stages
  • Real-Time Polymerase Chain Reaction

Substances

  • Cytokines
  • Interleukin-7