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Using human airway organoids, the study maps viral tropism, infection dynamics, and host cellular responses, and tests the antiviral potential of cidofovir. HAdV-14p1 robustly infects and replicates, with preferential targeting of ciliated, basal, and goblet cells. Infection markedly increases inflammatory mediators and activates p53-related and cytokine signaling programs, while reducing tight-junction and metabolic/oxidative phosphorylation pathways. Cidofovir suppresses replication with low organoid cytotoxicity.",{"@graph":69,"@context":122},[70,84,105],{"@type":71,"itemListElement":72},"BreadcrumbList",[73,77,79,82],{"item":74,"name":75,"@type":76,"position":8},"https://docshare.wps.com","Home","ListItem",{"item":78,"name":9,"@type":76,"position":14},"https://docshare.wps.com/document/",{"item":80,"name":35,"@type":76,"position":81},"https://docshare.wps.com/document/healthcare/",3,{"item":83,"name":65,"@type":76,"position":19},"https://docshare.wps.com/document/tropism-replication-competence-and-cellular-responses-of-hadv-14p1-in-human-airway-organoids/431977/",{"url":83,"name":65,"@type":85,"image":86,"author":91,"headline":65,"publisher":94,"fileFormat":97,"inLanguage":63,"description":67,"dateModified":98,"datePublished":99,"encodingFormat":97,"isAccessibleForFree":100,"interactionStatistic":101},"DigitalDocument",{"url":87,"@type":88,"width":89,"height":90},"https://docshare.wps.com/thumbnails/tropism-replication-competence-and-cellular-responses-of-hadv-14p1-in-human-airway-organoids/431977.png","ImageObject",300,407,{"name":92,"@type":93},"Adam","Person",{"url":74,"name":95,"@type":96},"DocShare","Organization","application/pdf","2026-10-29","2026-09-29",true,{"@type":102,"interactionType":103,"userInteractionCount":29},"InteractionCounter",{"@type":104},"ViewAction",{"@type":106,"mainEntity":107},"FAQPage",[108,114,118],{"name":109,"@type":110,"acceptedAnswer":111},"What model system was used to study HAdV-14p1?","Question",{"text":112,"@type":113},"The research used human airway organoids to characterize infection behavior and host cellular responses to HAdV-14p1.","Answer",{"name":115,"@type":110,"acceptedAnswer":116},"Which airway cell types are preferentially targeted by HAdV-14p1 in organoids?",{"text":117,"@type":113},"HAdV-14p1 robustly infected organoids, particularly targeting ciliated, basal, and goblet cells.",{"name":119,"@type":110,"acceptedAnswer":120},"How does cidofovir affect HAdV-14p1 replication and organoid viability?",{"text":121,"@type":113},"Cidofovir effectively inhibited viral replication while showing minimal cytotoxicity toward the organoids.","https://schema.org",{"og:url":83,"og:type":124,"og:title":65,"og:site_name":95,"og:description":67},"article",{"robots":126,"canonical":83},"index,follow",{"doc_id":128,"site_id":62},431977,1790693644,{"code":4,"msg":5,"data":131},{"doc_id":128,"user_id":132,"nickname":92,"user_avatar":133,"doc_module":4,"category_id":34,"category_name":35,"doc_title":65,"doc_description":67,"doc_content":134,"file_id":135,"file_url":136,"file_type":137,"file_size":138,"view_count":29,"is_deleted":4,"is_public":8,"is_downloadable":8,"audit_status":8,"page_count":139,"language":140,"language_code":63,"site_id":62,"html_lang":63,"table_of_contents":141,"faqs":142,"seo_title":143,"seo_description":67,"update_tm":144,"read_time":145,"preview_page_count":4},1374404737137,"https://ap-avatar.wpscdn.com/davatar_155a257f0dc6eb9ab79c44ca47cae57d","iScience Article  \nTropism, replication competence, and cellular  \nresponses of HAdV-14p1 in human airway organoids  \nAuthors  \nWenyu Guo, Yihao Yang, Ying Liang, ..., Lidong Liu, Yongping Lin, Qigao Chen  \nCorrespondence  \n[lidong.liu@gzhmu.eud.cn](lidong.liu@gzhmu.eud.cn) (L.L.),  \n[18928868278@163.com](18928868278@163.com) (Y.L.),  \n[734449359@qq.com](734449359@qq.com) (Q.C.)  \nIn brief  \nImmunology; Microbiology  \n• HAdV-14p1 activated inflammatory markers and weakened intercellular junctions  \n• Cidofovir inhibited HAdV-14p1 with minimal cytotoxicity toward organoids  \n• Human airway organoids represent a feasible model for human adenovirus research  \nGuo et al., 2026, iScience 29, 114323  \nJanuary 16, 2026 © 2025 The Authors. Published by Elsevier Inc.  \n[https://doi.org/10.1016/j.isci.2025.114323](https://doi.org/10.1016/j.isci.2025.114323)  \nll  \niScience  \nll  \nOPEN ACCESS  \nArticle  \nTropism, replication competence, and cellular responses of HAdV-14p1 in human airway organoids  \nWenyu Guo,1,2,5 Yihao Yang,1,2,5 Ying Liang,1,2,5 Fei Cui,3,5 Lianzhong Li,1,2 Xuechun Peng,1,2 Jing Zhou,1,2 Ya Li,1,2 Yuezhi Deng,1,2 Yixuan Wang,1,2 Rong Chen,1,2 Tao Wen,1,2 Cheng Lin,1,2 Weihong Lin,1,2 Lidong Liu,1,2,* Yongping Lin,4,* and Qigao Chen1,2,6,*  \n1Department of Laboratory Medicine, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou 510120, China  \n2Department of Clinical Laboratory, The Key Laboratory of Advanced Interdisciplinary Studies Center, The First Affiliated Hospital of Guangzhou Medical University, National Center for Respiratory Medicine, National Clinical Research Center for Respiratory Disease, Guangzhou 510120, China  \n3Department of Thoracic Surgery and Oncology, the First Affiliated Hospital of Guangzhou Medical University, State Key Laboratory of Respiratory Disease, National Clinical Research Center for Respiratory Disease, Guangzhou Institute of Respiratory Health, Guangzhou 510120, China  \n4Department of Laboratory Medicine, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital & Shenzhen Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Shenzhen 518100, China  \n5These authors contributed equally  \n6Lead contact  \n*Correspondence: [lidong.liu@gzhmu.eud.cn](lidong.liu@gzhmu.eud.cn) (L. L.), [18928868278@163.com](18928868278@163.com) (Y. L.), [734449359@qq.com](734449359@qq.com) (Q.C.) [https://doi.org/10.1016/j.isci.2025.114323](https://doi.org/10.1016/j.isci.2025.114323)  \nSUMMARY  \nHuman adenovirus type 14p1 (HAdV-14p1) is associated with severe respiratory illness. Using human airway organoids, we characterized the cellular tropism, infection dynamics, and cellular response to HAdV-14p1 , and evaluated the antiviral efficacy of cidofovir. HAdV-14p1 robustly infected and replicated in human airway organoids, particularly targeting ciliated, basal, and goblet cells. CCL5, CXCL10, CXCL11, and TNFSF13B were significantly upregulated upon HAdV-14p1 infection, indicating inflammatory activation. Pathway enrichment analysis revealed that upregulated genes were enriched in p53 signaling, cytokine-cytokine receptor interaction, and NOD-like receptor signaling pathways, whereas downregulated genes were linked to focal adhesion, tight junction, metabolic pathways, and oxidative phosphorylation pathways. Furthermore, treatment with cidofovir effectively inhibited viral replication with low cytotoxicity. Our findings highlight the robust replication and proinflammatory response that shape HAdV-14p1 pathogenesis and underscore the value of organoid systems in probing virus-host interactions and evaluating candidate antiviral strategies.  \nINTRODUCTION  \nHuman adenovirus (HAdV) is a highly contagious pathogen that causes a broad spectrum of clinical illnesses, including respiratory tract diseases, conjunctivitis, gastroenteritis, and urinary tract infections.1 At least 113 HAdV types are recognized ([http://hadvwg.gmu.edu/](http://hadvw","cbCaiaPGM0WjQ0O5","https://ap.wps.com/l/cbCaiaPGM0WjQ0O5","pdf",9814709,14,"English","# Summary\n# Introduction\n# Methods and Experimental Model\n# Viral Tropism and Infection Dynamics\n# Cellular and Pathway Responses\n# Antiviral Evaluation of Cidofovir\n# Discussion and Conclusions","[{\"question\":\"What model system was used to study HAdV-14p1?\",\"answer\":\"The research used human airway organoids to characterize infection behavior and host cellular responses to HAdV-14p1.\"},{\"question\":\"Which airway cell types are preferentially targeted by HAdV-14p1 in organoids?\",\"answer\":\"HAdV-14p1 robustly infected organoids, particularly targeting ciliated, basal, and goblet cells.\"},{\"question\":\"How does cidofovir affect HAdV-14p1 replication and organoid viability?\",\"answer\":\"Cidofovir effectively inhibited viral replication while showing minimal cytotoxicity toward the organoids.\"}]","Tropism, replication competence, and cellular responses of HAdV-14p1 in human airway organoids | PDF",1790657427,35]