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Viruses 2015, 7(8), 4230-4253; doi:10.3390/v7082817

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

1
Departments of Pediatrics, University of Alabama at Birmingham, PPS 102, 1600 5th Ave South, Birmingham, AL 35233, USA
2
Departments of Medicine, University of Alabama at Birmingham, PPS 102, 1600 5th Ave South, Birmingham, AL 35233, USA
3
Departments of Genetics, University of Alabama at Birmingham, PPS 102, 1600 5th Ave South, Birmingham, AL 35233, USA
4
Center for Global Health, Colorado School of Public Health, 13199 E Montview Blvd, Suite 310,A090 Aurora, CO 80045, USA
5
Cincinnati Children's Hospital Medical Center, 3333 Burnet Avenue, Cincinnati, OH 45229, USA
*
Author to whom correspondence should be addressed.
Academic Editor: Eric O. Freed
Received: 23 May 2015 / Revised: 14 July 2015 / Accepted: 17 July 2015 / Published: 30 July 2015
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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. View Full-Text
Keywords: respiratory syncytial virus; matrix metalloproteinase; cell; murine model respiratory syncytial virus; matrix metalloproteinase; cell; murine model
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This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. (CC BY 4.0).

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MDPI and ACS Style

Kong, M.Y.; Whitley, R.J.; Peng, N.; Oster, R.; Schoeb, T.R.; Sullender, W.; Ambalavanan, N.; Clancy, J.P.; Gaggar, A.; Blalock, J.E. Matrix Metalloproteinase-9 Mediates RSV Infection in Vitro and in Vivo. Viruses 2015, 7, 4230-4253.

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