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Most previous studies have relied on single\u2010omics or single\u2010model systems, limiting a comprehensive understanding of the dynamic and coordinated host response. To overcome this, we employed an integrated multiomics approach across complementary in vivo (murine) and physiologically relevant ex vivo (human bronchial organoid) models, combining longitudinal transcriptomic and proteomic profiling to systematically delineate the spatiotemporal dynamics of RSV\u2010induced lung injury and repair. Our analysis revealed a stage\u2010specific progression from early inflammatory injury to late repair, in which extracellular matrix (ECM)\u2013receptor interaction and PI3K\u2013Akt signaling play central roles. Moreover, a core set of hub genes including\n                    <jats:italic>Itgb3<\/jats:italic>\n                    ,\n                    <jats:italic>Itga2b<\/jats:italic>\n                    , and\n                    <jats:italic>Fn1<\/jats:italic>\n                    were positively correlated with RSV\u2010induced lung injury and clinical disease severity. Pharmacological inhibition of \u03b1IIb\u03b23 (encoded by\n                    <jats:italic>Itga2b<\/jats:italic>\n                    and\n                    <jats:italic>Itgb3<\/jats:italic>\n                    ) or fibronectin (\n                    <jats:italic>Fn1<\/jats:italic>\n                    ) in vivo significantly attenuated immunopathology and lung injury without affecting viral clearance, directly establishing their causal role in disease pathogenesis. Collectively, our study not only provides novel insights into the integrin\u2010centric network driving RSV immunopathology but also identifies a potential biomarker panel for clinical severity stratification and therapeutic targets for intervention.\n                  <\/jats:p>","DOI":"10.1002\/mco2.70811","type":"journal-article","created":{"date-parts":[[2026,7,1]],"date-time":"2026-07-01T17:07:36Z","timestamp":1782925656000},"source":"Crossref","is-referenced-by-count":0,"title":["Multiomics Identification and Validation of an Integrin\u2013Extracellular Matrix Network Driving Respiratory Syncytial Virus\u2010Induced Lung Injury and Repair"],"prefix":"10.1002","volume":"7","author":[{"given":"Lili","family":"Zhou","sequence":"first","affiliation":[{"name":"Center of Clinical Laboratory the First Affiliated Hospital of Soochow University  Suzhou China"},{"name":"The Institutes of Biology and Medical Science Suzhou Medical College Soochow University  Suzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hua","family":"Guo","sequence":"additional","affiliation":[{"name":"The Institutes of Biology and Medical Science Suzhou Medical College Soochow University  Suzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaofeng","family":"Yu","sequence":"additional","affiliation":[{"name":"The Institutes of Biology and Medical Science Suzhou Medical College Soochow University  Suzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yu","family":"Ran","sequence":"additional","affiliation":[{"name":"The Institutes of Biology and Medical Science Suzhou Medical College Soochow University  Suzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ruiqi","family":"Liu","sequence":"additional","affiliation":[{"name":"The Institutes of Biology and Medical Science Suzhou Medical College Soochow University  Suzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiali","family":"Zhu","sequence":"additional","affiliation":[{"name":"The Institutes of Biology and Medical Science Suzhou Medical College Soochow University  Suzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ran","family":"Li","sequence":"additional","affiliation":[{"name":"School of Medicine Hangzhou City University  Hangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jie","family":"Xu","sequence":"additional","affiliation":[{"name":"Center of Clinical Laboratory the First Affiliated Hospital of Soochow University  Suzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Leshi","family":"Chen","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Genetic Engineering School of Life Sciences Fudan University  Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yongliang","family":"Zhu","sequence":"additional","affiliation":[{"name":"Laboratory of Gastroenterology Department Second Affiliated Hospital of Zhejiang University School of Medicine  Hangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Long","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Radiation Oncology and the State Key Laboratory of Transvascular Implantation Devices, The Second Affiliated Hospital of Zhejiang University School of Medicine, Life Sciences Institute Zhejiang University Hangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhenjiang","family":"Bai","sequence":"additional","affiliation":[{"name":"Pediatric Intensive Care Unit Children's Hospital of Soochow University  Suzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fangfang","family":"Zhou","sequence":"additional","affiliation":[{"name":"Center of Clinical Laboratory the First Affiliated Hospital of Soochow University  Suzhou China"},{"name":"The Institutes of Biology and Medical Science Suzhou Medical College Soochow University  Suzhou China"},{"name":"Biomedical Basic Research Center (BBRC) of Jiangsu Province  Suzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,7,1]]},"reference":[{"key":"e_1_2_11_2_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa0804877"},{"issue":"18","key":"e_1_2_11_3_1","first-page":"1792","article-title":"Viral Bronchiolitis in Children","volume":"374","author":"Rossi G. 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