Matrix metalloproteinase expression correlates with virulence following neurotropic mouse hepatitis virus infection.
The relationship(s) between viral virulence and matrix metalloproteinase (MMP) expression in the central nervous system (CNS) of mice undergoing lethal and sublethal infections with neurotropic mouse hepatitis virus was investigated. Lethal infection induced increased levels of MMP-3 and MMP-12 mRNAs as well as that of tissue inhibitor of matrix metalloproteinases 1 (TIMP-1) compared to sublethal infection. Increased induction of MMP, TIMP, and chemokine expression correlated with increased virus replication but not with inflammatory cell infiltration. Infection of immunosuppressed mice suggested that expression of most MMP, TIMP, and chemokine mRNA was induced primarily in CNS-resident cells. By contrast, MMP-9 protein activity was associated with the infiltration of neutrophils into the CNS. These data indicate an association between the magnitude of inflammatory gene expression within the CNS and viral virulence.
Zhou
Jiehao
J
Department of Pathology, Keck School of Medicine, University of Southern California, Los Angeles, California 90033, USA.
Stohlman
Stephen A
SA
Atkinson
Roscoe
R
Hinton
David R
DR
Marten
Norman W
NW
D000818:Animals; D001921:Brain / Q000821:virology; D020805:Central Nervous System Viral Diseases / Q000276:immunology / Q000401:mortality / Q000503:physiopathology* / Q000821:virology*; D018352:Coronavirus Infections / Q000276:immunology / Q000401:mortality / Q000503:physiopathology / Q000821:virology; D005434:Flow Cytometry; D007249:Inflammation; D008297:Male; D053508:Matrix Metalloproteinase 12; D019278:Matrix Metalloproteinase 3 / Q000378:metabolism*; D008666:Metalloendopeptidases / Q000378:metabolism*; D051379:Mice; D008807:Mice, Inbred BALB C; D006517:Murine hepatitis virus / Q000472:pathogenicity*; D019715:Tissue Inhibitor of Metalloproteinase-1 / Q000378:metabolism*; D014774:Virulence
D019715:Tissue Inhibitor of Metalloproteinase-1; D008666:Metalloendopeptidases; D019278:Matrix Metalloproteinase 3; D053508:Matrix Metalloproteinase 12