We found a match
Your institution may have access to this item. Find your institution then sign in to continue.
- Title
Matrix Metalloproteinase-9 Mediates RSV Infection in Vitro and in Vivo.
- Authors
Kong, Michele Y. F.; Whitley, Richard J.; Ning Peng; Oster, Robert; Schoeb, Trenton R.; Sullender, Wayne; Ambalavanan, Namasivayam; Clancy, John Paul; Gaggar, Amit; Blalock, J. Edwin
- 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.
- Subjects
MATRIX metalloproteinases; RESPIRATORY syncytial virus infections; PATHOGENIC microorganisms; LABORATORY mice; AIRWAY resistance (Respiration)
- Publication
Viruses (1999-4915), 2015, Vol 7, Issue 8, p1
- ISSN
1999-4915
- Publication type
Article
- DOI
10.3390/v70x0000x