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  3. Determination of the effects of Herpes simplex glycoprotein B on epigenetic alterations in in vitro models of Alzheimer's disease

Determination of the effects of Herpes simplex glycoprotein B on epigenetic alterations in in vitro models of Alzheimer's disease

  • J Alzheimers Dis. 2026 Apr;110(4):1886-1898. doi: 10.1177/13872877261427784.
Anil Yirün 1 2,  Deniz Arca Çakır 3,  Selinay Başak Erdemli Köse 1 4,  Aylin Balcı Özyurt 1 5,  Göksun Demirel 2,  Pinar Erkekoglu 1 3
Affiliations

Affiliations

  • 1 Department of Pharmaceutical Toxicology, Hacettepe University Faculty of Pharmacy, Altındag/Ankara, Turkey.
  • 2 Department of Pharmaceutical Toxicology, Cukurova University Faculty of Pharmacy, Sarıçam/Adana, Turkey.
  • 3 Department of Vaccine Technology, Hacettepe University Vaccine Institute, Altındag/Ankara, Turkey.
  • 4 Department of Chemistry, Burdur Mehmet Akif Ersoy University Faculty of Arts and Sciences, Merkez/Burdur, Turkey.
  • 5 Department of Pharmaceutical Toxicology, Bahçeşehir University Faculty of Pharmacy, Beşiktaş/Istanbul, Turkey.
PMID: 41823023 DOI: 10.1177/13872877261427784
Abstract

BackgroundEpigenetic dysregulation is increasingly recognized as a key mechanism in the development and progression of Alzheimer's disease (AD). Herpes simplex virus type 1 (HSV-1) Infection has been proposed as a potential biological trigger that may accelerate neurodegeneration through epigenetic modifications. Among HSV-1 structural proteins, glycoprotein B (HSV-gB) may influence host-virus interactions affecting neuronal gene regulation.ObjectiveThis study aimed to investigate the contribution of HSV-gB to AD-related epigenetic alterations and to determine whether HSV-gB exposure exacerbates epigenetic dysregulation in two in vitro neuronal AD models.MethodsHuman SH-SY5Y neuroblastoma cells were used to establish two AD models: a differentiation-based aging model induced by retinoic acid and brain-derived neurotrophic factor (RA + BDNF), and an amyloid aggregation model induced by Amyloid-β 1-42 (Aβ1-42). Cells were treated with HSV-gB (190.5 pg/ml) alone or in combination with each model. Global DNA methylation, histone H3 and H4 acetylation, histone multiplex modifications, and HDAC3 and HDAC8 levels were analyzed using ELISA-based assays.ResultsHSV-gB exposure and RA + BDNF treatment induced global DNA hypomethylation and histone hypoacetylation, accompanied by significant increases in HDAC3 and HDAC8 levels. In contrast, the Aβ1-42 model showed DNA hypermethylation and histone hyperacetylation, indicating distinct epigenetic profiles between differentiation-associated aging and amyloid-driven pathology.ConclusionsHSV-gB contributes to AD-related epigenetic dysregulation and may amplify neurodegenerative mechanisms through HDAC-mediated chromatin remodeling. The findings highlight divergent epigenetic signatures in different AD models and support a potential role for viral factors in modulating AD-associated epigenetic pathways.

Keywords

Alzheimer's disease; DNA methylation; epigenetic alterations; herpes simplex virus; histone modifications.

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