Epstein-barr virus and multiple sclerosis: from pathogenesis and diagnosis to EBV-specific T cell therapy and...

Multiple sclerosis (MS) is a central nervous system (CNS) disorder defined by inflammation, demyelination, and neuronal damage. Several independent studies have confirmed the prevalence of EBV infection in MS and the presence of elevated anti-EBV antibody titers in serum prior to and throughout the clinical period of MS. EBV stands out from other human-infecting viruses in that it can activate, infect, and clone the B cells and remain a latent infection inside them. The prevalence of EBV-positive B cell lymphoproliferative diseases in immunocompromised individuals demonstrates the critical significance of immune surveillance in managing EBV infection. It has also been postulated that a deficiency in EBV-specific CD8⁺ T cell regulation predisposes to MS by allowing EBV-infected autoreactive B cells and plasma cells to concentrate in the CNS. Thus, EBV-specific T-cell therapy might have the potential to eradicate B lymphocytes infected by EBV in the CNS, preventing disease development and leading to enhanced clinical outcomes. One of the effective approaches for treating MS patients is application of EBV-specific T cells. In this method, peripheral blood mononuclear cells (PBMCs) are isolated from patients and expanded with EBV-specific antigens, resulting in antiviral cytotoxic response. This review discusses the significance of EBV in the pathogenesis of MS, the impact of disease-modifying T-cell treatments targeting EBV, therapeutic implications to target EBV in MS pathogenesis, and several novel EBV-targeting gene therapies.