Altered EBV specific immune control in multiple sclerosis

• Published in: Journal of neuroimmunology 2024-05, Vol.390, p.578343, Article 578343
• Main Author: Münz, Christian
• Format: Article
• Language: English
• Subjects: EBNA1; Epstein-Barr virus; Infectious mononucleosis; Multiple sclerosis; NK cells; T cells
• ISSN: 0165-5728; 1872-8421; 1872-8421
• DOI: 10.1016/j.jneuroim.2024.578343

Since the 1980s it is known that immune responses to the Epstein-Barr virus (EBV) are elevated in multiple sclerosis (MS) patients. Recent seroepidemiologial data have shown that this alteration after primary EBV infection identifies individuals with a more than 30-fold increased risk to develop MS. The mechanisms by which EBV infection might erode tolerance for the central nervous system (CNS) in these individuals, years prior to clinical MS onset, remain unclear. In this review I will discuss altered frequencies of EBV life cycle stages and their tissue distribution, EBV with CNS autoantigen cross-reactive immune responses and loss of immune control for autoreactive B and T cells as possible mechanisms. This discussion is intended to stimulate future studies into these mechanisms with the aim to identify candidates for interventions that might correct EBV specific immune control and/or resulting cross-reactivities with CNS autoantigens in MS patients and thereby ameliorate disease activity. •Recent seroepidemiological evidence suggests that EBV infection initiates prodromal MS disease in susceptible individuals.•Frequency of EBV life cycle stages and their tissue distribution might be altered in MS patients.•Cross-reactive antibody and T cell responses between EBV antigens and myelin autoantigens have been observed in MS patients.•Immune control of autoreactive B and T cell responses might be compromised by EBV infection and improved by HCMV infection.•Alterations of EBV infection and immune control in MS patients could be targeted for disease modification.