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.