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

Mouse hepatitis virus (MHV; m-B-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-B-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-B-CoV infected mice brain. Our study revealed that m-B-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-B-CoV-induced neuroinflammation.