Type-I interferons induce lung protease responses following respiratory syncytial virus infection via RIG-I-like receptors

R F Foronjy, C C Taggart, A J Dabo, S Weldon, N Cummins, P Geraghty

Research output: Contribution to journalArticlepeer-review

24 Citations (Scopus)
204 Downloads (Pure)

Abstract

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. Mavs-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.

Original languageEnglish
Pages (from-to)161-175
JournalMucosal immunology
Volume8
Issue number1
Early online date09 Jul 2014
DOIs
Publication statusPublished - Jan 2015

Fingerprint Dive into the research topics of 'Type-I interferons induce lung protease responses following respiratory syncytial virus infection via RIG-I-like receptors'. Together they form a unique fingerprint.

Cite this