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A critical aspect of this hijacking involves the reprogramming of host cell metabolism. This review summarizes current findings on how influenza virus infection alters major metabolic pathways, including enhanced glycolysis, suppression of oxidative phosphorylation, diversion of TCA cycle intermediates for biosynthesis, and upregulation of lipid and amino acid metabolism. Key nutrients like glucose, glutamine, and serine are redirected to support viral RNA synthesis, protein production, and membrane formation. Moreover, these metabolic changes also modulate host immune responses, potentially aiding in immune evasion. We highlight the role of transcription factors such as SREBPs in lipid synthesis and the impact of one-carbon metabolism on epigenetic regulation. Finally, we discuss how targeting virus-induced metabolic shifts, using agents like 2-deoxyglucose or fatty acid synthesis inhibitors, offers promising avenues for antiviral intervention, while emphasizing the need for selective approaches to minimize harm to normal cells.<\/jats:p>","DOI":"10.3390\/v17101386","type":"journal-article","created":{"date-parts":[[2025,10,17]],"date-time":"2025-10-17T16:13:03Z","timestamp":1760717583000},"page":"1386","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":11,"title":["Metabolic Hostile Takeover: How Influenza Virus Reprograms Cellular Metabolism for Replication"],"prefix":"10.3390","volume":"17","author":[{"given":"Xianfeng","family":"Hui","sequence":"first","affiliation":[{"name":"Department of Immunology, School of Basic Medical Sciences, Henan Medical University, Xinxiang 453003, China"},{"name":"Xinxiang Engineering Technology Research Center of Immune Checkpoint Drug for Liver-Intestinal Tumors, Henan Medical University, Xinxiang 453003, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaowei","family":"Tian","sequence":"additional","affiliation":[{"name":"Department of Pathogenic Biology, School of Basic Medical Sciences, Henan Medical University, Xinxiang 453003, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shihuan","family":"Ding","sequence":"additional","affiliation":[{"name":"Department of Immunology, School of Basic Medical Sciences, Henan Medical University, Xinxiang 453003, China"},{"name":"Xinxiang Engineering Technology Research Center of Immune Checkpoint Drug for Liver-Intestinal Tumors, Henan Medical University, Xinxiang 453003, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ge","family":"Gao","sequence":"additional","affiliation":[{"name":"Henan Collaborative Innovation Center of Molecular Diagnosis and Laboratory Medicine, School of Medical Technology, Henan Medical University, Xinxiang 453003, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xin","family":"Zhao","sequence":"additional","affiliation":[{"name":"Department of Immunology, School of Basic Medical Sciences, Henan Medical University, Xinxiang 453003, China"},{"name":"Xinxiang Engineering Technology Research Center of Immune Checkpoint Drug for Liver-Intestinal Tumors, Henan Medical University, Xinxiang 453003, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiyan","family":"Cui","sequence":"additional","affiliation":[{"name":"Department of Immunology, School of Basic Medical Sciences, Henan Medical University, Xinxiang 453003, China"},{"name":"Xinxiang Engineering Technology Research Center of Immune Checkpoint Drug for Liver-Intestinal Tumors, Henan Medical University, Xinxiang 453003, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yiru","family":"Hou","sequence":"additional","affiliation":[{"name":"Department of Immunology, School of Basic Medical Sciences, Henan Medical University, Xinxiang 453003, China"},{"name":"Xinxiang Engineering Technology Research Center of Immune Checkpoint Drug for Liver-Intestinal Tumors, Henan Medical University, Xinxiang 453003, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tiesuo","family":"Zhao","sequence":"additional","affiliation":[{"name":"Department of Immunology, School of Basic Medical Sciences, Henan Medical University, Xinxiang 453003, China"},{"name":"Xinxiang Engineering Technology Research Center of Immune Checkpoint Drug for Liver-Intestinal Tumors, Henan Medical University, Xinxiang 453003, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2454-3814","authenticated-orcid":false,"given":"Hui","family":"Wang","sequence":"additional","affiliation":[{"name":"Henan Collaborative Innovation Center of Molecular Diagnosis and Laboratory Medicine, School of Medical Technology, Henan Medical University, Xinxiang 453003, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,10,17]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1128","DOI":"10.1126\/science.adt0180","article-title":"A single mutation in bovine influenza H5N1 hemagglutinin switches specificity to human receptors","volume":"386","author":"Lin","year":"2024","journal-title":"Science"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"e0078622","DOI":"10.1128\/jvi.00786-22","article-title":"PSMD12-Mediated M1 Ubiquitination of Influenza A Virus at K102 Regulates Viral Replication","volume":"96","author":"Hui","year":"2022","journal-title":"J. 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