Project R-11248

Epstein-Barr virus and multiple sclerosis risk: does imprinting of monocytes provide better explanations? (Research)

Multiple sclerosis (MS) is a devastating chronic inflammatory disease of the central nervous system (CNS). While it has a high prevalence, its etiology is still poorly understood. MS is a multifactorial disease caused by a combination of genetic, immunological and environmental factors. The best documented and most strongly associated environmental risk factor for MS is Epstein-Barr virus (EBV). However, it is yet not known how EBV exactly contributes to the development of MS. We propose that EBV imprinted monocytes could play a central role in the increased susceptibility for MS. In a pilot study we confirmed that murid gammaherpesvirus 4 (MuHV-4) infection leads to a worse clinical outcome in an experimental MS model (EAE) compared to mock infected animals. First, we investigate the contribution of monocytes in the MuHV-4 induced worsening of EAE by characterisation of the CNS infiltrating monocytes and of the CNS-resident myeloid cells. Then, we will find evidence for a causal role of imprinted monocytes in the worsening of EAE. Finally, to provide human translation of the results obtained in mice, we check for EBV-associated monocyte modifications in human MS blood samples and post-mortem CNS brain material. Altogether, these approaches will contribute to a better understanding on how EBV increases overall MS risk and thus warrant the development of EBV target therapies for MS.

01 November 2020 - 31 October 2022