The Role of Metalloproteinases in Corona Virus Infection

Infection with neurotropic strains of mouse hepatitis virus (MHV) results in rapid leukocyte infiltration into the central nervous system (CNS). The inflammatory response controls virus replication but fails to mediate sterile clearance. The persistence of viral RNA and inflammatory cells within the CNS is associated with the development of ongoing demyelination. Matrix metalloproteinases (MMPs) are a family of proteases involved in degradation of the extracellular matrix (ECM). During inflammatory responses MMPs are thought to play a significant role in breaking down the basement membrane surrounding blood vessels as well as parenchymal ECM thereby facilitating leukocyte infiltration. MMPs have also been associated with activation of chemokines and perhaps more significantly the degradation of myelin proteins and generation of autoantigens. Recent examination of MMP expression during MHV infection suggests that MMP-3, -9 and -12 are involved in the inflammatory response. The proinflammatory effects of these MMPs are likely tempered by induction of tissue inhibiter of metalloproteinase-1 expression.