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bioRxiv · 10.64898/2026.09.02.748627

Matrilysin (MMP-7) Restricts RSV Infection and Airway Inflammation through Proteolysis of CCR3 and RSV-G

LAMKHIOUED, B.
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Abstract

Airway epithelium forms a frontline barrier against microbial invasion through mucociliary clearance and the secretion of antimicrobial and immunomodulatory mediators. Matrix metalloproteinases (MMPs), traditionally viewed as tissue-remodelling enzymes, are also implicated in inflammatory processes and are recognized for their capacity to shap host-pathogen interactions. This study investigates the role of MMP-7 (matrilysin) in airway inflammation and the pathogenesis of respiratory syncytial virus (RSV) infection. In silico analyses predicted that MMP-7 binds CCR3, the receptor for eotaxin-1/CCL11, and that it also engages the region of the RSV G protein that docks onto CCR3, pointing to a shared biochemical mechanism interfering with both chemokine binding and viral attachment. Mechanistically, MMP-7 proteolytically cleaved CCR3, disrupting eotaxin-1/CCL11 binding and reducing eosinophil activation and chemotaxis, whereas CX3CR1 was unaffected. Importantly, biophysical measurements confirmed that MMP-7 binds and cleaves the RSV G protein, consequently restricting RSV entry and replication in airway epithelial cells. In vivo, MMP-7-deficient mice displayed higher RSV infection, exacerbated airway inflammation and increased mucus production following RSV challenge. Collectively, these findings identify MMP-7 as a key epithelial antiviral effector coordinating both antiviral defense and the regulation of pulmonary inflammation.

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LAMKHIOUED, B.. 2026-09-06. Matrilysin (MMP-7) Restricts RSV Infection and Airway Inflammation through Proteolysis of CCR3 and RSV-G. https://doi.org/10.64898/2026.09.02.748627

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