Abstract
Epstein-Barr virus (EBV) is an important environmental risk factor in the development of several autoimmune conditions, with the mechanisms still to be fully elucidated. EBV primarily infects memory B cells, transitioning between lytic (active) and latent (dormant) phases of infection. Our group has previously proposed two molecular mechanisms linking EBV pathogenesis to autoimmunity: one indicates that EBV lytic switching contributes to systemic lupus erythematosus (SLE) pathogenesis, while another posits that latency III is more crucial in the development of multiple sclerosis (MS). In this study, we tested the proposed molecular model using a cohort of EBV-transformed lymphoblastoid cell lines derived from individuals with either SLE, MS or healthy controls. Measuring the expression levels of a panel of EBV genes, representing the different phases of the EBV lifecycle, we found compelling proof-of-concept evidence validating our proposed model. This discovery highlights promising signatures for further investigation, where the same approach can be explored across other EBV-associated immune conditions, deepening our understanding of the virus's lifecycle dysregulation in autoimmunity etiology and ultimately aiding in the design of new treatments.