Respiratory viruses as key drivers of pulmonary fibrosis: integrated pathways from barrier injury to immune-fibrotic crosstalk.

Pulmonary fibrosis (PF), a highly heterogeneous form of interstitial lung disease, presents substantial challenges for both basic research and clinical management due to its complex pathogenesis and poor clinical outcomes. In recent years, PF induced by respiratory viral infections has emerged as a forefront topic in respiratory medicine. However, the dynamic regulatory network linking virus-mediated alveolar epithelial injury, aberrant tissue repair, and fibroblast activation remains incompletely understood. This review focuses on representative respiratory viruses-including Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), seasonal influenza viruses, and highly pathogenic avian influenza viruses-and analyzes, from multiple mechanistic dimensions, how viral infection drives the development of PF. The article analyzes how viral infections contribute to tissue damage and functional loss in the lungs via direct host-cell injury, dysregulated immune responses, and disturbances in epigenetic regulation. In particular, the review highlights the aberrant activation of the transforming growth factor-β (TGF-β)/Smad signaling pathway and virus-induced polarization of alveolar macrophages as key processes in the progression of fibrosis. Furthermore, this review systematically summarizes the shared molecular pathways triggered by viral infections in the development of PF and their potential biomarkers, providing a theoretical basis for targeted therapies. In conclusion, respiratory viruses are not only significant etiological factors in PF, but also accelerate the fibrotic process through immune-fibrotic interactions. This review provides a theoretical framework for a deeper understanding of virus-induced PF and outlines directions for the development of targeted therapies and clinical intervention strategies.