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

Academic Article

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.
  • Published In

  • Viruses  Journal
  • Keywords

  • cell, matrix metalloproteinase, murine model, respiratory syncytial virus, Animals, Cells, Cultured, Epithelial Cells, Gene Silencing, Host-Pathogen Interactions, Humans, Lung, Matrix Metalloproteinase 9, Mice, Inbred C57BL, Mice, Knockout, RNA, Small Interfering, Respiratory Syncytial Viruses, Viral Load
  • Digital Object Identifier (doi)

    Author List

  • Kong MYF; Whitley RJ; Peng N; Oster R; Schoeb TR; Sullender W; Ambalavanan N; Clancy JP; Gaggar A; Blalock JE
  • Start Page

  • 4230
  • End Page

  • 4253
  • Volume

  • 7
  • Issue

  • 8