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However, the role of vagal\u2010\u03b17 nAChR signaling in influenza virus infection is unclear. In particular, does vagal\u2010\u03b17 nAChR signaling impact the infection of alveolar epithelial cells (AECs), the primary target cells of influenza virus? Here, we demonstrated a distinct role of \u03b17 nAChR in type II AECs compared to its role in immune cells during influenza infection. We found that deletion of <jats:italic>Chrna7<\/jats:italic> (encoding gene of \u03b17 nAChR) in type II AECs or disruption of vagal circuits reduced lung influenza infection and protected mice from influenza\u2010induced lung injury. We further unveiled that activation of \u03b17 nAChR enhanced influenza infection through PTP1B\u2010NEDD4L\u2010ASK1\u2010p38MAPK pathway. Mechanistically, activation of \u03b17 nAChR signaling decreased p38MAPK phosphorylation during infection, facilitating the nuclear export of influenza viral ribonucleoproteins and thereby promoting infection. Taken together, our findings reveal a mechanism mediated by vagal\u2010\u03b17 nAChR signaling that promotes influenza viral infection and exacerbates disease severity. Targeting vagal\u2010\u03b17 nAChR signaling may offer novel strategies for combating influenza virus infections.<\/jats:p>","DOI":"10.1002\/jmv.29768","type":"journal-article","created":{"date-parts":[[2024,7,9]],"date-time":"2024-07-09T06:02:18Z","timestamp":1720504938000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Vagal\u2010\u03b17 nicotinic acetylcholine receptor signaling exacerbates influenza severity by promoting lung epithelial cell infection"],"prefix":"10.1002","volume":"96","author":[{"given":"Caiqi","family":"Zhao","sequence":"first","affiliation":[{"name":"Unit of Respiratory Infection and Immunity, Shanghai Institute of Immunity and Infection, Chinese Academy of Sciences University of Chinese Academy of Sciences Shanghai China"},{"name":"Department of Respiratory and Critical Care Medicine, Shanghai Pulmonary Hospital, School of Medicine Tongji University Shanghai China"},{"name":"University of Chinese Academy of Sciences Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mengyao","family":"Pan","sequence":"additional","affiliation":[{"name":"Unit of Respiratory Infection and Immunity, Shanghai Institute of Immunity and Infection, Chinese Academy of Sciences University of Chinese Academy of Sciences Shanghai China"},{"name":"University of Chinese Academy of Sciences Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jie","family":"Chen","sequence":"additional","affiliation":[{"name":"Unit of Respiratory Infection and Immunity, Shanghai Institute of Immunity and Infection, Chinese Academy of Sciences University of Chinese Academy of Sciences Shanghai China"},{"name":"University of Chinese Academy of Sciences Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ling","family":"Li","sequence":"additional","affiliation":[{"name":"Unit of Respiratory Infection and Immunity, Shanghai Institute of Immunity and Infection, Chinese Academy of Sciences University of Chinese Academy of Sciences Shanghai China"},{"name":"University of Chinese Academy of Sciences Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yan","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Hematology, Shanghai General Hospital Shanghai Jiao Tong University School of Medicine Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wenjun","family":"Liu","sequence":"additional","affiliation":[{"name":"Institute of Microbiology Chinese Academy of Sciences Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael A.","family":"Matthay","sequence":"additional","affiliation":[{"name":"Department of Medicine, Department of Anesthesia, Cardiovascular Research Institute University of California San Francisco San Francisco California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Haichao","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Emergency Medicine North Shore University Hospital Manhasset New York USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xia","family":"Jin","sequence":"additional","affiliation":[{"name":"Shanghai Serum Bio\u2010Technology Co., Ltd. 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