Entanglement of Epstein-BARR virus with Alzheimer’s disease

Abstract

Epstein-Barr virus (EBV) is a member of herpesviridae and is the first known oncogenic virus. The virus undergoes both latent and lytic cycles. Infrequent reactivation of the virus from the latent cycle causes a serious health condition called infectious mononucleosis (IM) or glandular fever. Patients suffering from IM are found to be at a high risk for Alzheimer’s disease (AD) but the mechanism is still elusive. The present study deals with understanding the unrevealed association of EBV with AD. A 12-amino-acid containing peptide derived from EBV glycoprotein M (gM), 146SYKHVFLSAFVY157 accelerated the aggregation of Aβ42. Exposing the neuronal cells to EBV and gM146-157 was capable of initiating inflammatory response in vitro. Additionally, the exposure significantly altered the mitochondrial biology by decreasing the mitochondrial membrane potential (MMP). Besides, exposure to EBV and gM146-157 manifested upregulation in the synthesis of amyloid precursor peptide (APP) and Apolipoprotein E (ApoE4) in the in-vitro system. Subsequently, intranasal administration of EBV and gM146-157 exposed IMR-32 have significantly increased the anxiety like behaviour in female Swiss albino mice. Taken together, the study underlined the mysterious association of EBV with neuroinflammation, mitochondrial dysfunction and ultimately AD. Key words: Alzheimer’s disease, Amyloid beta, Amyloid precursor protein, Apolipoprotein E, Epstein-Barr virus, Glycoprotein M