title: Type-I interferons induce lung protease responses following respiratory syncytial virus infection via RIG-I-like receptors.
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.
authors.affiliation: Department of Medicine, Mount Sinai Roosevelt Hospital, Mount Sinai Health System, Division of Pulmonary and Critical Care Medicine, New York, New York, USA.
authors.forename: R F
authors.initials: RF
authors.lastname: Foronjy
authors.affiliation: Centre for Infection and Immunity, School of Medicine, Dentistry and Biomedical Sciences, Queen's University Belfast, Belfast, UK.
authors.forename: C C
authors.initials: CC
authors.lastname: Taggart
authors.affiliation: Department of Medicine, Mount Sinai Roosevelt Hospital, Mount Sinai Health System, Division of Pulmonary and Critical Care Medicine, New York, New York, USA.
authors.forename: A J
authors.initials: AJ
authors.lastname: Dabo
authors.affiliation: Centre for Infection and Immunity, School of Medicine, Dentistry and Biomedical Sciences, Queen's University Belfast, Belfast, UK.
authors.forename: S
authors.initials: S
authors.lastname: Weldon
authors.affiliation: Department of Medicine, Mount Sinai Roosevelt Hospital, Mount Sinai Health System, Division of Pulmonary and Critical Care Medicine, New York, New York, USA.
authors.forename: N
authors.initials: N
authors.lastname: Cummins
authors.affiliation: Department of Medicine, Mount Sinai Roosevelt Hospital, Mount Sinai Health System, Division of Pulmonary and Critical Care Medicine, New York, New York, USA.
authors.forename: P
authors.initials: P
authors.lastname: Geraghty
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics / Q000378:metabolism*; D033942:Adaptor Proteins, Vesicular Transport / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D002403:Cathepsins / Q000378:metabolism*; D000071457:DEAD Box Protein 58; D053487:DEAD-box RNA Helicases / Q000235:genetics / Q000502:physiology*; D015967:Gene Expression Regulation, Viral; D007370:Interferon Type I / Q000276:immunology; D007930:Leucine / Q000008:administration & dosage / Q000031:analogs & derivatives; D008168:Lung / Q000201:enzymology* / Q000821:virology; D020782:Matrix Metalloproteinases / Q000378:metabolism*; D051379:Mice; D008815:Mice, Inbred Strains; D018345:Mice, Knockout; D010649:Phenylalanine / Q000008:administration & dosage / Q000031:analogs & derivatives; D018357:Respiratory Syncytial Virus Infections / Q000188:drug therapy / Q000276:immunology*; D012136:Respiratory Syncytial Viruses / Q000187:drug effects / Q000276:immunology*; D012254:Ribavirin / Q000008:administration & dosage; D013876:Thiophenes / Q000008:administration & dosage; D019562:Viral Load / Q000187:drug effects
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D033942:Adaptor Proteins, Vesicular Transport; D002403:Cathepsins; D000071457:DEAD Box Protein 58; D053487:DEAD-box RNA Helicases; D007370:Interferon Type I; D007930:Leucine; D020782:Matrix Metalloproteinases; D010649:Phenylalanine; D012254:Ribavirin; D013876:Thiophenes; C512612:MAVS protein, mouse; C476286:Ticam1 protein, mouse; C080985:batimastat; C503356:Ddx58 protein, mouse; C024974:E 64