{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T14:45:38Z","timestamp":1785422738694,"version":"3.56.0"},"reference-count":40,"publisher":"MDPI AG","issue":"6","license":[{"start":{"date-parts":[[2026,6,3]],"date-time":"2026-06-03T00:00:00Z","timestamp":1780444800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"crossref","award":["82573493"],"award-info":[{"award-number":["82573493"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"crossref","award":["82172707"],"award-info":[{"award-number":["82172707"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"crossref"}]},{"award":["82573493"],"award-info":[{"award-number":["82573493"]}],"id":[{"id":"https:\/\/ror.org\/01h0zpd94","id-type":"ROR","asserted-by":"publisher"}]},{"award":["82172707"],"award-info":[{"award-number":["82172707"]}],"id":[{"id":"https:\/\/ror.org\/01h0zpd94","id-type":"ROR","asserted-by":"publisher"}]},{"name":"Guangzhou National Laboratory","award":["GZNL2024A01001"],"award-info":[{"award-number":["GZNL2024A01001"]}]},{"award":["GZNL2024A01001"],"award-info":[{"award-number":["GZNL2024A01001"]}],"id":[{"id":"https:\/\/ror.org\/03ybmxt82","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Viruses"],"abstract":"<jats:p>Cathepsin C (CTSC) is a major lysosomal cysteine protease characterized by its involvement in multiple essential pathological processes associated with various viral infections and pathogenesis, such as influenza virus and coronavirus. However, the antiviral spectrum of CTSC and the molecular mechanisms underlying its activity remain to be fully elucidated. In this study, we demonstrate that CTSC significantly inhibits the infection of influenza A virus (IAV) H1N1 both in vitro and in vivo. Mechanistically, the antiviral function of CTSC is associated with attenuation of the PI3K-AKT signaling pathway, thereby inducing cell apoptosis and reducing inflammation, which ultimately limits the virus\u2019s ability to hijack host resources. Taken together, our findings highlight the crucial role of CTSC in defense against H1N1 by targeting PI3K-AKT pathway and suggest a prospective antiviral target against the infection of H1N1.<\/jats:p>","DOI":"10.3390\/v18060641","type":"journal-article","created":{"date-parts":[[2026,6,3]],"date-time":"2026-06-03T18:08:07Z","timestamp":1780510087000},"page":"641","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Cathepsin C Restricts Influenza A Virus Replication and Is Associated with Suppression of the PI3K-AKT Signaling Pathway"],"prefix":"10.3390","volume":"18","author":[{"given":"Yansheng","family":"Zhu","sequence":"first","affiliation":[{"name":"College of Life Sciences, Anhui Medical University, Hefei 230032, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lanlan","family":"Si","sequence":"additional","affiliation":[{"name":"Graduate School, Guangzhou Medical University, Guangzhou 511436, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhongzhong","family":"Cao","sequence":"additional","affiliation":[{"name":"College of Life Sciences, Hebei University, Baoding 071002, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Huiyang","family":"Song","sequence":"additional","affiliation":[{"name":"Academy of Military Medical Sciences, Beijing 100850, China"},{"name":"State Key Laboratory of Medical Proteomics, National Center for Protein Sciences at Beijing, Beijing 100850, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aiqing","family":"Yang","sequence":"additional","affiliation":[{"name":"Academy of Military Medical Sciences, Beijing 100850, China"},{"name":"State Key Laboratory of Medical Proteomics, National Center for Protein Sciences at Beijing, Beijing 100850, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xia","family":"Wang","sequence":"additional","affiliation":[{"name":"Academy of Military Medical Sciences, Beijing 100850, China"},{"name":"State Key Laboratory of Medical Proteomics, National Center for Protein Sciences at Beijing, Beijing 100850, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yifei","family":"Qiu","sequence":"additional","affiliation":[{"name":"Academy of Military Medical Sciences, Beijing 100850, China"},{"name":"State Key Laboratory of Medical Proteomics, National Center for Protein Sciences at Beijing, Beijing 100850, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chengming","family":"Gao","sequence":"additional","affiliation":[{"name":"Academy of Military Medical Sciences, Beijing 100850, China"},{"name":"State Key Laboratory of Medical Proteomics, National Center for Protein Sciences at Beijing, Beijing 100850, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gangqiao","family":"Zhou","sequence":"additional","affiliation":[{"name":"College of Life Sciences, Anhui Medical University, Hefei 230032, China"},{"name":"Graduate School, Guangzhou Medical University, Guangzhou 511436, China"},{"name":"College of Life Sciences, Hebei University, Baoding 071002, China"},{"name":"Academy of Military Medical Sciences, Beijing 100850, China"},{"name":"State Key Laboratory of Medical Proteomics, National Center for Protein Sciences at Beijing, Beijing 100850, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pengbo","family":"Cao","sequence":"additional","affiliation":[{"name":"Academy of Military Medical Sciences, Beijing 100850, China"},{"name":"State Key Laboratory of Medical Proteomics, National Center for Protein Sciences at Beijing, Beijing 100850, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,6,3]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"60","DOI":"10.1038\/nrmicro.2017.146","article-title":"Erratum: The evolution of seasonal influenza viruses","volume":"16","author":"Petrova","year":"2017","journal-title":"Nat. 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