Matrix Metalloproteinase-9 Mediates RSV Infection in Vitro and in Vivo.
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| Abstract |
Respiratory Syncytial Virus (RSV) is an important human pathogen associated with substantial morbidity and mortality. The present study tested the hypothesis that RSV infection would increase matrix metalloproteinase (MMP)-9 expression, and that MMP-9 inhibition would decrease RSV replication both in vitro and in vivo. RSV A2 infection of human bronchial epithelial cells increased MMP-9 mRNA and protein release. Cells transfected with siRNA against MMP-9 following RSV infection had lower viral titers. In RSV infected wild-type (WT) mice, MMP-9, airway resistance and viral load peaked at day 2 post infection, and remained elevated on days 4 and 7. RSV infected MMP-9 knockout (KO) mice had decreased lung inflammation. On days 2 and 4 post inoculation, the RSV burden was lower in the MMP-9 KO mice compared to WT controls. In conclusion, our studies demonstrate that RSV infection is a potent stimulus of MMP-9 expression both in vitro and in vivo. Reduction of MMP-9 (via siRNA knockdown, and in MMP-9 KO mice) resulted in decreased viral replication. Our findings suggest MMP-9 is a potential therapeutic target for RSV disease.
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| Authors | Michele Y F Kong, Richard J Whitley, Ning Peng, Robert Oster, Trenton R Schoeb, Wayne Sullender, Namasivayam Ambalavanan, John Paul Clancy, Amit Gaggar, J Edwin Blalock |
| Journal | Viruses (Viruses) Vol. 7 Issue 8 Pg. 4230-53 (Jul 30 2015) ISSN: 1999-4915 [Electronic] Switzerland |
| PMID | 26264019 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, Non-P.H.S., Research Support, U.S. Gov't, P.H.S.) |
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