Chemokines in Coronavirus-Induced Demyelination

Trifilo, Matthew J.; Liu, Michael T.; Glass, William G.; Lane, Thomas E.

Inflammation within the central nervous system (CNS) is critical in the development of the neuropathology associated with the human demyelinating disease multiple sclerosis (MS). Recent studies have identified a family of soluble proinflammatory molecules called chemokines that are able to direct leukocyte infiltration into the CNS in response to infection or injury. Identification of chemokines within and around demyelinating lesions in MS patients indicate a potential role for these molecules in contributing to the pathogenesis of MS. To address this issue, we have used mouse hepatitis virus (MHV) infection of the CNS to understand the dynamic interaction of chemokine expression as it relates to inflammation and neuropathology. Our results indicate that chemokine expression within the CNS results in persistent recruitment of both T lymphocytes and macrophages and results in subsequent myelin destruction. Herein, we demonstrate the complexity of the chemokine response to MHV infection of the CNS and the delicate balance that exists between host defense and development of disease.