Respiratory syncytial virus infection induces matrix metalloproteinase-9 expression in epithelial cells.
Increased gelatinolytic activity was observed in respiratory syncytial virus (RSV)-infected HEp-2 cells by using zymography. The anti-matrix metalloproteinase-9 (MMP-9) antibody specifically reduced the gelatinolytic activity suggesting that the increased gelatinolytic activity was due to the MMP-9. It was also supported by the results from immunofluorescent staining, treatment of MMP inhibitors, and RSV infection of the cell clones that were transfected with plasmids to express more MMP-9 and tissue type inhibitor of metalloproteinase-1 (TIMP-1). The gelatinolytic activity of extracellular MMP-9 in RSV-infected HEp-2 cells increased 1.5 +/- 0.2 fold compared with the control (p < 0.01). Cell surface MMP-9 expression was also clearly detected by immunofluorescent staining. Treatment with 1,10-phenanthroline (0.05 mM), ethylenediamine-tetraacetate (EDTA) (1.5 mM), and penta-O-galloyl-beta-D-glucose (PGG) (3.3 microM) inhibited RSV multiplication as well as syncytia formation. Furthermore, the average syncytia size increased when the cells expressing more MMP-9 were infected by RSV. In contrast, syncytia formation was inhibited in the cells manipulated to express TIMP-1. Thus, this study concludes that although RSV infection induces MMP-9, which can enhance the syncytia formation leading to RSV multiplication and spread it can be inhibited by MMP inhibitors.
Yeo
S J
SJ
Department of Microbiology and Cancer Research Institute, SNUMRC, Seoul National University College of Medicine, Korea.
Yun
Y J
YJ
Lyu
M A
MA
Woo
S Y
SY
Woo
E R
ER
Kim
S J
SJ
Lee
H J
HJ
Park
H K
HK
Kook
Y H
YH
D004847:Epithelial Cells / Q000378:metabolism* / Q000821:virology; D015726:Giant Cells / Q000502:physiology; D006801:Humans; D020780:Matrix Metalloproteinase 9 / Q000235:genetics / Q000378:metabolism*; D061965:Matrix Metalloproteinase Inhibitors; D018357:Respiratory Syncytial Virus Infections / Q000821:virology*; D012136:Respiratory Syncytial Viruses / Q000472:pathogenicity* / Q000502:physiology; D019715:Tissue Inhibitor of Metalloproteinase-1 / Q000235:genetics / Q000378:metabolism; D014162:Transfection; D014407:Tumor Cells, Cultured; D014779:Virus Replication
D061965:Matrix Metalloproteinase Inhibitors; D019715:Tissue Inhibitor of Metalloproteinase-1; D020780:Matrix Metalloproteinase 9