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It connects metabolic targets to how influenza replication proceeds within immune cells and explains the role of kinases as key regulators of glucose metabolism and immune mediation. Mechanistic focus includes the Warburg effect and the PFK1/PFKFB3 glycolysis rate-controlling complex, plus mTOR signaling in multiple immune cell types. The work argues that modulating immune-linked metabolic checkpoints or kinases may support future immunotherapy and calls for systems-level models clarifying host outcomes and immune-metabolic crosstalk.",{"@graph":69,"@context":123},[70,84,106],{"@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/glucose-metabolism-and-innate-immune-responses-in-influenza-virus-infection-mechanistic-insights-and-clinical-perspectives/465375/",{"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/glucose-metabolism-and-innate-immune-responses-in-influenza-virus-infection-mechanistic-insights-and-clinical-perspectives/465375.png","ImageObject",300,407,{"name":92,"@type":93},"Rhys","Person",{"url":74,"name":95,"@type":96},"DocShare","Organization","application/pdf","2026-10-31","2026-09-30",true,{"@type":102,"interactionType":103,"userInteractionCount":105},"InteractionCounter",{"@type":104},"ViewAction",12,{"@type":107,"mainEntity":108},"FAQPage",[109,115,119],{"name":110,"@type":111,"acceptedAnswer":112},"How does influenza infection affect glucose metabolism in immune cells?","Question",{"text":113,"@type":114},"Influenza infection drives metabolic alterations that influence immune cell responses, including shifts in glycolysis-related pathways and related signaling activity.","Answer",{"name":116,"@type":111,"acceptedAnswer":117},"What mechanisms are highlighted regarding glycolysis regulation?",{"text":118,"@type":114},"The review highlights the Warburg effect, lactate production during infection, and the PFK1/PFKFB3 enzyme complex as a rate-determining regulator of glycolysis.",{"name":120,"@type":111,"acceptedAnswer":121},"Why is targeting metabolic checkpoints or kinases considered promising for therapy?",{"text":122,"@type":114},"Modulating immune-associated metabolic changes may influence disease progression, and kinase/metabolic targets could open avenues for future immunotherapy against influenza.","https://schema.org",{"og:url":83,"og:type":125,"og:title":65,"og:site_name":95,"og:description":67},"article",{"robots":127,"canonical":83},"index,follow",{"doc_id":129,"site_id":62},465375,1790825531,{"code":4,"msg":5,"data":132},{"doc_id":129,"user_id":133,"nickname":92,"user_avatar":134,"doc_module":4,"category_id":34,"category_name":35,"doc_title":65,"doc_description":67,"doc_content":135,"file_id":136,"file_url":137,"file_type":138,"file_size":139,"view_count":105,"is_deleted":4,"is_public":8,"is_downloadable":8,"audit_status":8,"page_count":46,"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":31,"preview_page_count":4},687207024643,"https://ap-avatar.wpscdn.com/davatar_3d24733baf745e90a7e4bdd5f77d97b2","Review  \nGlucose Metabolism and Innate Immune Responses in Influenza Virus Infection: Mechanistic Insights and Clinical Perspectives  \nKareem Awad 1,2,3, *, Nancy N. Shahin 4, Tarek K. Motawi 4, Maha Abdelhadi 5, Reham F. Barghash 6, Ahmed M. Awad 7, Laura Kakkola 1,8 and Ilkka Julkunen 1,8,9  \nAcademic Editor: Alessandro Poggi  \nReceived: 30 October 2025  \nRevised: 16 December 2025  \nAccepted: 21 December 2025  \nPublished: 26 December 2025  \nCopyright: © 2025 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license.  \n1 Institute of Biomedicine, Faculty of Medicine, University of Turku, 20520 Turku, Finland;  \nlaura.kakkola@utu.fi (L.K.); ilkka.julkunen@utu.fi (I.J.)  \n2 Academy of Scientific Research & Technology-Short Term Applied Research & Technology Transfer (ASRT-STARS), Cairo 11516, Egypt  \n3 Institute of Pharmaceutical and Drug Industries Research, National Research Centre, Giza 12622, Egypt  \n4 Biochemistry Department, Faculty of Pharmacy, Cairo University, Kasr El-Aini, Cairo 11562, Egypt; [nancy.shahin@pharma.cu.edu.eg](nancy.shahin@pharma.cu.edu.eg) (N.N.S.); [tarek.motawi@pharma.cu.edu.eg](tarek.motawi@pharma.cu.edu.eg) (T.K.M.)  \n5 Internal Medicine Department, Institute of Medical Research and Clinical Studies, National Research Center, Giza 12622, Egypt; [mahahadi39@yahoo.com](mahahadi39@yahoo.com)  \n6 Institute of Chemical Industries Research, National Research Centre, Giza 12622, Egypt; [reham_fawzy@yahoo.com](reham_fawzy@yahoo.com)  \n7 Research and Innovation Office, California State University Channel Islands, Camarillo, CA 93012, USA; [ahmed.awad@csuci.edu](ahmed.awad@csuci.edu)  \n8 Clinical Microbiology, Turku University Hospital, 20521 Turku, Finland  \n9 InFLAMES Research Flagship, University of Turku, 20014 Turku, Finland  \n* Correspondence: [kareem.awad@web.de](kareem.awad@web.de)  \nAbstract  \nThis review article discusses glucose metabolic alterations affecting immune cell responses to influenza virus infection. It highlights possible relationships between essential metabolic targets and influenza replication dynamics in immune cells. Thus, kinases as essential regulators of glucose metabolism as well as critical immune mediators during this infection such as interferons, tumor necrosis factor-alpha and transforming growth factor beta have been illustrated. Mechanistic highlights are provided for both the Warburg effect, where glycolysis shifts to lactate production during influenza infection, and the PFK1/PFKFB3 enzyme complex as the rate-determining regulator of glycolysis whose activity increases during the course of influenza infection. The mechanisms of mammalian target of rapamycin (mTOR) signaling as a promotor of glycolysis and a regulator of inflammatory cytokine production are discussed across various immune cell types during infection. We conclude that modulation of the metabolic changes associated with immune responses plays an important role in disease progression, and that targeting metabolic checkpoints or kinases may offer promising avenues for future immunotherapy approaches for the treatment of influenza virus infection. We also emphasize the need for further research to develop a comprehensive biological model that clarifies host outcomes and the complex nature of immune-metabolic regulation and crosstalk.  \nKeywords: influenza; immune-metabolism; glucose metabolism; host-pathogen interactions; therapeutic targets; kinases  \n1. Introduction  \nInfluenza is a communicable viral disease characterized by acute respiratory illness that causes annual epidemics leading to 3–5 million severe cases within approximately  \n5–15% of the world’s population infected with the virus [1,2] . The surface of the influenzavirus particle displays three key proteins: hemagglutinin (HA), neuraminidase (NA), and M2 protein [3] . These glycoproteins are essential for viral infecti","cbCaihrJxVHSzCpw","https://ap.wps.com/l/cbCaihrJxVHSzCpw","pdf",1118637,"English","# Introduction\n## Influenza as a communicable respiratory disease\n## Clinical features and severe complications\n## Antiviral treatment and prevention strategies","[{\"question\":\"How does influenza infection affect glucose metabolism in immune cells?\",\"answer\":\"Influenza infection drives metabolic alterations that influence immune cell responses, including shifts in glycolysis-related pathways and related signaling activity.\"},{\"question\":\"What mechanisms are highlighted regarding glycolysis regulation?\",\"answer\":\"The review highlights the Warburg effect, lactate production during infection, and the PFK1/PFKFB3 enzyme complex as a rate-determining regulator of glycolysis.\"},{\"question\":\"Why is targeting metabolic checkpoints or kinases considered promising for therapy?\",\"answer\":\"Modulating immune-associated metabolic changes may influence disease progression, and kinase/metabolic targets could open avenues for future immunotherapy against influenza.\"}]","Glucose Metabolism and Innate Immune Responses in Influenza Virus Infection - Mechanistic Insights and Clinical Perspectives | PDF",1790769548]