Type-I interferons induce lung protease responses following respiratory syncytial virus infection via RIG-I-like receptors
Data(s) |
01/01/2015
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Resumo |
<p>The role of proteases in viral infection of the lung is poorly understood. Thus, we examined matrix metalloproteinases (MMPs) and cathepsin proteases in respiratory syncytial virus (RSV)-infected mouse lungs. RSV-induced gene expression for MMPs -2, -3, -7, -8, -9, -10, -12, -13, -14, -16, -17, -19, -20, -25, -27, and -28 and cathepsins B, C, E, G, H, K, L1, S, W, and Z in the airways of Friend leukemia virus B sensitive strain mice. Increased proteases were present in the bronchoalveolar lavage fluid (BALF) and lung tissue during infection. Mitochondrial antiviral-signaling protein (MAVS) and TIR-domain-containing adapter-inducing interferon-β-deficient mice were exposed to RSV. <i>Mavs</i>-deficient mice had significantly lower expression of airway MMP-2, -3, -7, -8, -9, -10, -12, -13, and -28 and cathepsins C, G, K, S, W, and Z. In lung epithelial cells, retinoic acid-inducible gene-1 (RIG-I) was identified as the major RIG-I-like receptor required for RSV-induced protease expression via MAVS. Overexpression of RIG-I or treatment with interferon-β in these cells induced MMP and cathepsin gene and protein expression. The significance of RIG-1 protease induction was demonstrated by the fact that inhibiting proteases with batimastat, E64 or ribavirin prevented airway hyperresponsiveness and enhanced viral clearance in RSV-infected mice.</p> |
Identificador |
http://dx.doi.org/10.1038/mi.2014.54 http://pure.qub.ac.uk/ws/files/42151404/Manuscript_for_Green_Access.pdf |
Idioma(s) |
eng |
Direitos |
info:eu-repo/semantics/openAccess |
Fonte |
Foronjy , R F , Taggart , C C , Dabo , A J , Weldon , S , Cummins , N & Geraghty , P 2015 , ' Type-I interferons induce lung protease responses following respiratory syncytial virus infection via RIG-I-like receptors ' Mucosal Immunology , vol 8 , pp. 161-175 . DOI: 10.1038/mi.2014.54 |
Tipo |
article |
Formato |
application/pdf |