Matrix metalloproteinases and tissue inhibitors of metalloproteinases in murine β-coronavirus-induced neuroinflammation

Abstract

Mouse hepatitis virus (MHV; m-β-CoV) serves as a useful model for studying the cellular factors involved in neuroinflammation. To understand the role of matrix metalloproteinases (MMPs) in neuroinflammation, brain tissues from m-β-CoV-infected mice were harvested at different days post-infection (d.p.i) and investigated for Mmp expression by RT-qPCR. Mmp-2, -3, -8, -12 showed significant mRNA upregulation peaking with viral replication between 5 and 6 d.p.i. Elevated levels of MMP regulator TIMP-1 are suggestive of a TIMP-1 mediated host antiviral response. Biological network assessment suggested a direct involvement of MMP-3, -8, -14 in facilitating peripheral leukocyte infiltrations. Flow cytometry confirmed the increased presence of NK cells, CD4⁺ and CD8⁺ T cells, neutrophils, and MHCII expressing cells in the m-β-CoV infected mice brain. Our study revealed that m-β-CoV upregulated Park7, RelA, Nrf2, and Hmox1 transcripts involved in ROS production and antioxidant pathways, describing the possible nexus between oxidative pathways, MMPs, and TIMP in m-β-CoV-induced neuroinflammation.

Keywords: MHV-A59; MMPs; Neuroinflammation; ROS; TIMPs; β-coronavirus (β-CoV).