Neurotropic murine coronavirus mediated demyelination: Factors dampening pathogenesis

Abstract

Virus infections and autoimmune responses are implicated as primary triggers of demyelinating diseases. Specifically, the association of Epstein-Barr virus (EBV) infection with development of multiple sclerosis (MS) has re-ignited an interest in virus induced autoimmune responses to CNS antigens. Nevertheless, demyelination may also be caused by immune mediated bystander pathology in an attempt to control direct infection in the CNS. Tissue damage as a result of anti-viral responses or low level viral persistence may lead to immune activation manifesting in demyelinating lesions, axonal damage and clinical symptoms. This review focuses on the neurotropic mouse coronavirus induced demyelination model to highlight how immune responses activated during the acute phase pave the way to dampen pathology and promote repair. We specifically discuss the role of immune dampening factors programmed cell death ligand 1 (PD-L1) and interleukin (IL)-10, as well as microglia and triggering receptor expressed on myeloid cells 2 (Trem2), in limiting demyelination independent of viral persistence.