From viral epigenetic reprogramming to neuroinflammation: Mechanisms driving neurodegeneration.
From viral epigenetic reprogramming to neuroinflammation: Mechanisms driving neurodegeneration.
Where did the research take place?
The study site has not been established. Author addresses may differ from where the research occurred.
Indore, IN · Author affiliation
Infection Bioengineering Group, Mehta Family School of Biosciences and Biomedical Engineering, Indian Institute of Technology Indore, Simrol, Indore, Madhya Pradesh, 453552, India.Location evidence
Munich, DE · Author affiliation
Technical University of Munich (TUM), Klinikum rechts der Isar, Ismaningerstr. 22, 81675, Munich, Germany.Location evidence
Saint Petersburg, RU · Author affiliation
Laboratory of Biomedical Nanotechnologies, Institute of Cytology, Russian Academy of Sciences (RAS), Tikhoretsky Ave. 4, Saint Petersburg, 194064, Russia.Location evidence
Rome, IT · Author affiliation
Department of Experimental Medicine, Sapienza University of Rome, Rome, 00161, Italy.Location evidence
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Original abstract
Viruses exploit host genetic machinery to establish chronic infections and contribute to chronic neurodegenerative and immune disorders. By manipulating DNA methylation, histone modifications, and non-coding RNA networks, viruses such as Epstein-Barr virus (EBV), Herpes Simplex virus (HSV), Zika virus (ZIKV), and Human immunodeficiency virus (HIV) induce epigenetic changes that silence or delay the host antiviral defenses and reprogram host gene expression. For instance, EBV recruits DNA methyltransferases (DNMTs) to hypermethylate genes such as SOCS1 while ZIKV disrupts neuronal DNA methylation via heterochromatinization. Concurrently, HIV-1 encoded Tat protein disrupts H3K27 acetylation in astrocytes that potently triggers glutamate excitotoxicity. Viruses also subvert the chromatin architecture to modulate 3D interactions and reader protein recruitment, thus rewiring transcriptional programs. Such epigenetic alterations correlate with neuropathologies wherein global hypomethylation and histone acetylation contribute to Alzheimer's or Parkinson's disease. Although several mechanisms are known, the field of viral control in neuroepigenetics is underexplored. Emerging therapies that target viral-host epigenetic crosstalk through DNMT or HDAC inhibitors are promising. This review highlights how neurotropic viruses co-opt epigenetic pathways to drive neurodegeneration. We also explore biomarker-driven strategies for personalized interventions in neurodegenerative disorders thus emphasizing potential epigenetic editing tools to restore neuronal homeostasis.