{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,15]],"date-time":"2026-10-15T00:45:02Z","timestamp":1792025102301,"version":"4.4.0"},"reference-count":45,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,5,20]],"date-time":"2026-05-20T00:00:00Z","timestamp":1779235200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100003725","name":"National Research Foundation of Korea","doi-asserted-by":"publisher","award":["RS-2024-00452828, 2021M3H9A1030260, RS-2024-00443043, RS-2026-25494200"],"award-info":[{"award-number":["RS-2024-00452828, 2021M3H9A1030260, RS-2024-00443043, RS-2026-25494200"]}],"id":[{"id":"10.13039\/501100003725","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:sec>\n                    <jats:title>Introduction<\/jats:title>\n                    <jats:p>SARS-CoV-2 and influenza A virus (IAV) cause viral pneumonia, yet their lung lesions evolve with distinct spatial organization and resolution-phase architecture. In preclinical murine studies, H&amp;amp;E histopathology is a primary endpoint, but burden-focused semiquantitative scoring can miss pathogen- and phase-specific differences in lesion topology, compartmental involvement, inflammatory organization, and repair. We aimed to define virus- and phase-specific morphologic signatures and translate them into a practical, pathogenesis-informed scoring guide, supported by whole-slide convolutional neural network (CNN) analysis with class activation mapping (CAM).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Mice were infected under standardized conditions and evaluated during the early, peak-injury, and late phases of infection, corresponding to 2~3, 5~8, and 14 days post-infection (dpi), respectively. Lungs were assessed by H&amp;amp;E with semiquantitative scoring and by immunostaining to map viral antigen distribution and epithelial tropism. Whole-slide CNN models were trained for virus- and phase-specific classification, and CAM localized discriminative regions.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Dose titration established reproducible lethal and sublethal infection conditions for both viruses. Viral antigen kinetics diverged, with SARS-CoV-2 peaking early and declining toward clearance by the resolution phase, whereas IAV peaked later and declined by the resolution phase, paralleling distinct injury\u2013repair trajectories. CNN\/CAM analysis distinguished virus- and phase-specific histologic patterns across the early, peak-injury, and resolution phases of infection and highlighted spatial signatures consistent with expert review. At the peak-injury phase, SARS-CoV-2 lungs showed broad alveolar\/interstitial involvement, whereas IAV exhibited bronchocentric inflammatory organization. During the resolution phase, IAV showed prominent epithelial regeneration with remodeling-forward architecture, while SARS-CoV-2 more often retained localized residual inflammatory foci. Across both infections, tissue inflammatory composition shifted over time, with higher neutrophil representation during the peak-injury phase and a relative increase in lymphocytic representation during the resolution phase. Integrating lesion topology\/distribution, edema, epithelial injury\u2013regeneration, remodeling features, and lymphocyte predominance, we proposed a pathogen-resolved, phase-informed histopathology scoring guide with recommended evaluation windows for each model.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Together, these findings define virus- and phase-specific morphologic programs that inform respiratory virus pathogenesis in mice and can be translated into practical scoring criteria for preclinical respiratory virus studies.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fimmu.2026.1826608","type":"journal-article","created":{"date-parts":[[2026,5,20]],"date-time":"2026-05-20T13:23:35Z","timestamp":1779283415000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":1,"title":["Deep learning\u2013assisted, pathogenesis-informed lung histopathology scoring in preclinical mouse models of SARS-CoV-2 and influenza A infection"],"prefix":"10.3389","volume":"17","author":[{"given":"Hyeok-Won","family":"An","sequence":"first","affiliation":[{"name":"Department of Laboratory Animal Medicine, College of Veterinary Medicine, Seoul National University","place":["Seoul, Republic of Korea"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hyeon Ah","family":"Kim","sequence":"additional","affiliation":[{"name":"Department of Laboratory Animal Medicine, College of Veterinary Medicine, Seoul National University","place":["Seoul, Republic of Korea"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tae Hun","family":"Ha","sequence":"additional","affiliation":[{"name":"Department of Laboratory Animal Medicine, College of Veterinary Medicine, Seoul National University","place":["Seoul, Republic of 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