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Here, we used immunostaining, genetic, and pharmacological approaches to determine whether IAV\u2010induced cellular senescence causes prolonged alterations in lungs. Mice infected with a sublethal dose of H1N1p2009 exhibited cellular senescence, as evidenced by increased pulmonary expression of p16, p21, \u03b2\u2010galactosidase and the DNA damage marker gamma\u2010H2A.X. Cellular senescence began 4\u2009days post\u2010infection (dpi) in the bronchial epithelium, then spread to the lung parenchyma by 7 and 28\u2009dpi (long after viral clearance), and then declined by 90\u2009dpi. At 28\u2009dpi, the lungs showed severe remodeling with structural bronchial and alveolar lesions, abrasion of the airway epithelium, and pulmonary emphysema and fibrotic lesions that persisted up to 90\u2009dpi. In mice and nonhuman primates, persistence of senescent cells in the bronchial wall on 28 dpi was associated with abrasion of the airway epithelium. In p16\u2010ATTAC mice, depletion of p16\u2010expressing cells with AP20187 reduced pulmonary emphysema and fibrosis and led to complete recovery of the airway epithelium at 28\u2009dpi, indicating a marked acceleration of the epithelial repair process. Treatment with the senolytic drug ABT\u2010263 also accelerated epithelial repair without affecting pulmonary fibrosis or emphysema. These positive effects occurred independently of viral clearance and lung inflammation at 7\u2009dpi. Finally, AP20187 treatment of p16\u2010ATTAC mice at 15\u2009dpi led to complete recovery of the airway epithelium at 28\u2009dpi. Thus, virus\u2010induced senescent cells contribute to the pulmonary sequelae of influenza; targeting senescent cells may represent a new preventive therapeutic option.<\/jats:p>","DOI":"10.1111\/acel.70140","type":"journal-article","created":{"date-parts":[[2025,6,20]],"date-time":"2025-06-20T22:17:11Z","timestamp":1750457831000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["Virus\u2010Induced Cellular Senescence Causes Pulmonary Sequelae Post\u2010Influenza Infection"],"prefix":"10.1111","volume":"24","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7998-8378","authenticated-orcid":false,"given":"Larissa","family":"Lipskaia","sequence":"first","affiliation":[{"name":"Institut Mondor de Recherche Biom\u00e9dicale (IMRB), FHU SENEC Univ. 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