INTERPLAY BETWEEN VIRUSES AND B CELLS IN THE PATHOGENESIS OF MULTIPLE SCLEROSIS.

Multiple sclerosis (MS) is a chronic progressive autoimmune neurological disease and the most common demyelinating disorder in Western countries. Although significant progress has been made in providing new therapeutic strategies, identification of definitive triggers for MS has proven elusive. Many factors are known to be involved, including UVB levels and vitamin-D and Human endogenous retrovirus (HERV). However, recent studies have shown Epstein-Barr Virus (EBV) is the single biggest risk factor for MS Importantly, their contribution to the pathogenesis of MS remains unknown. In this project we aim to understand how EBV, B cell differentiation status and innate immunity co-operate to trigger reactivation of HERV-W in B cells. Thereafter, using B cells from the cerebrospinal fluid of MS patients, we will explore how these factors co-operate to generate cross-reactive antibodies targeting both viral proteins and MS autoimmune targets, including myelin. By pinning down how the viruses contribute to the pathogenesis of MS, we will open-up badly needed new treatment and prevention avenues for the disease, principally aimed at controlling the triggering causes rather than just modifying the later immune damage.