Unraveling the Connection of Epstein-Barr Virus and Its Glycoprotein M Peptide with Neurological Ailments.

Epstein-Barr virus (EBV) is known to be associated with several cancers along with neurological modalities like Alzheimer's disease (AD) and multiple sclerosis (MS). Previous study from our group revealed that a 12 amino acid peptide fragment (SYKHVFLSAFVY) of EBV glycoprotein M (gM) exhibits amyloid-like self-aggregative properties. In the current study, we have investigated its effect on Aβ aggregation along with its effect on neural cell immunology and disease markers. EBV virion was also considered for the above-mentioned investigation. An increase in the aggregation of Aβ peptide was observed upon incubation with gM. Further, the exposure of EBV and gM onto neuronal cells indicated the upregulation of inflammatory molecules like IL-1β, IL-6, TNF-α, and TGF-β that suggested neuroinflammation. Besides, host cell factors like mitochondrial potential and calcium ion signaling play a crucial role in cellular homeostasis and alterations in these factors aid in neurodegeneration. Changes in mitochondrial membrane potential manifested a decrease while elevation in the level of total Ca ions was observed. Amelioration of Ca ions triggers excitotoxicity in neurons. Subsequently, neurological disease-associated genes APP, ApoE4, and MBP were found to be increased at the protein level. Additionally, demyelination of neurons is a hallmark of MS and the myelin sheath consists of ∼70% of lipid/cholesterol-associated moieties. Hereby, genes associated with cholesterol metabolism indicated changes at the mRNA level. Enhanced expression of neurotropic factors like NGF and BDNF was discerned postexposure to EBV and gM. Altogether, this study delineates a direct connection of EBV and its peptide gM with neurological illnesses.