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

Area of Science:

• Virology
• Immunology
• Pulmonology

Background:

• The role of proteases in lung viral infections, specifically respiratory syncytial virus (RSV), is not well understood.
• Matrix metalloproteinases (MMPs) and cathepsin proteases are key enzymes involved in various physiological and pathological processes.

Purpose of the Study:

• To investigate the expression and role of MMPs and cathepsins in the context of RSV infection in mouse lungs.
• To elucidate the signaling pathways, particularly RIG-I-like receptors (RLRs), involved in RSV-induced protease expression.

Main Methods:

• Analysis of MMP and cathepsin gene expression in RSV-infected mouse lungs.
• Comparison of protease expression in wild-type, MAVS-deficient, and RIG-I-overexpressing lung epithelial cells upon RSV exposure.
• Assessment of the impact of protease inhibition on airway hyperresponsiveness and viral clearance in RSV-infected mice.

Main Results:

• RSV infection significantly upregulated numerous MMPs and cathepsins in mouse airways, bronchoalveolar lavage fluid, and lung tissue.
• Mice deficient in MAVS showed markedly reduced expression of several RSV-induced proteases.
• RIG-I was identified as the critical RLR mediating RSV-induced protease expression via MAVS, with interferon-β also inducing these proteases.

Conclusions:

• RSV infection triggers the expression of a wide array of MMPs and cathepsins in the lung through the RIG-I/MAVS pathway.
• Inhibition of these induced proteases offers a potential therapeutic strategy to mitigate RSV-induced airway hyperresponsiveness and enhance viral clearance.