Exploring the enigmatic role of EPSTEIN-BARR virus in neuroinflammation and neurodegeneration associated with Alzheimer’s disease

Abstract

The members of the Herpesviridae family have long been known for their neuroinvasive potential and are linked with various disorders of the Central nervous system (CNS), such as encephalitis, neuritis, cerebral lymphoma, myelitis, etc. [1]. However, the neurotropic potential of the Human Herpesvirus 4 (HHV-4) in particular has only been recently established in-vitro [2], [3]. HHV-4, also known as Epstein-Barr virus (EBV), is primarily considered an oncogenic lymphotropic virus that infects B-cells and epithelial cells to establish lifelong latency. It has been prominently associated with a heterogeneous group of malignancies such as Burkitt’s, Hodgkin’s, non-Hodgkin’s lymphoma, nasopharyngeal carcinoma, gastric cancer adenocarcinomas, etc. [4]. Though EBV’s ability to cause neurodegeneration has been debated for decades, multiple clinical and in-vivo studies have recently provided convincing evidence of its involvement in neurodegenerative disorders (NDDs) like multiple sclerosis (MS), Alzheimer’s (AD), Parkinson’s disease (PD), chronic fatigue syndrome (CFS), and so on [5]. Various studies have reported a robust anti-EBV antibody response in the serological and cerebrospinal fluid (CSF) samples collected from patients suffering from NDDs, thus indicating a strong association between EBV and NDDs [6], [7].