Matrix Metalloproteinase-9 Mediates RSV Infection in Vitro and in Vivo

• Main 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
• Format: Article
• Language: English
• Published: MDPI AG 2015-07-01
• Series: Viruses
• Subjects: respiratory syncytial virus; matrix metalloproteinase; cell; murine model
• Online Access: http://www.mdpi.com/1999-4915/7/8/2817

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.