{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,25]],"date-time":"2026-05-25T02:03:32Z","timestamp":1779674612827,"version":"3.53.1"},"reference-count":98,"publisher":"MDPI AG","issue":"11","license":[{"start":{"date-parts":[[2026,5,23]],"date-time":"2026-05-23T00:00:00Z","timestamp":1779494400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Glutamine is the most abundant amino acid in human plasma and tissues and plays essential roles in cellular metabolism, biosynthesis, and redox homeostasis. Beyond these canonical functions, glutamine availability and utilization have emerged as key regulators of multiple cellular stress responses, including the integrated stress response, endoplasmic reticulum stress, metabolic checkpoint signaling, and autophagy. During viral infection, host glutamine metabolism is frequently reprogrammed to meet the energetic and biosynthetic demands of viral replication, thereby inducing or reshaping glutamine-linked stress pathways. Increasing evidence indicates that these stress responses are not merely secondary consequences of infection but actively influence key stages of the viral life cycle, including viral entry, genome replication, protein synthesis, and host antiviral responses. In this review, we summarize current advances in understanding how glutamine metabolism regulates cellular stress responses in the context of both viral and non-viral infections, and how these pathways, in turn, modulate viral pathogenesis and host defense. We discuss the context-dependent roles of glutamine-linked stress signaling in either promoting viral replication or restricting infection, depending on viral species, host cell type, and metabolic conditions. Finally, we highlight emerging concepts and unresolved questions, including the potential of targeting glutamine metabolism and associated stress pathways as host-directed antiviral strategies. A deeper understanding of the interplay between glutamine metabolism, cellular stress responses, and viral infection may provide new insights into disease mechanisms and inform the development of novel therapeutic approaches.<\/jats:p>","DOI":"10.3390\/ijms27114717","type":"journal-article","created":{"date-parts":[[2026,5,25]],"date-time":"2026-05-25T01:45:08Z","timestamp":1779673508000},"page":"4717","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Glutamine-Linked Cellular Stress Responses in Viral Infection: Mechanisms, Crosstalk, and Future Perspectives"],"prefix":"10.3390","volume":"27","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9719-0159","authenticated-orcid":false,"given":"Ngan Thi Kim","family":"Pham","sequence":"first","affiliation":[{"name":"Department of Applied Molecular Chemistry, College of Industrial Technology, Nihon University, Chiba 274-0072, Japan"},{"name":"Division of Microbiology, Department of Pathology and Microbiology, Nihon University School of Medicine, Tokyo 173-8610, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5610-1570","authenticated-orcid":false,"given":"Quang Duy","family":"Trinh","sequence":"additional","affiliation":[{"name":"Division of Microbiology, Department of Pathology and Microbiology, Nihon University School of Medicine, Tokyo 173-8610, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4378-3861","authenticated-orcid":false,"given":"Hiroshi","family":"Ushijima","sequence":"additional","affiliation":[{"name":"Division of Microbiology, Department of Pathology and Microbiology, Nihon University School of Medicine, Tokyo 173-8610, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9417-0315","authenticated-orcid":false,"given":"Shihoko","family":"Komine-Aizawa","sequence":"additional","affiliation":[{"name":"Division of Microbiology, Department of Pathology and Microbiology, Nihon University School of Medicine, Tokyo 173-8610, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kazuaki","family":"Yoshimune","sequence":"additional","affiliation":[{"name":"Department of Applied Molecular Chemistry, College of Industrial Technology, Nihon University, Chiba 274-0072, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,5,23]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1002\/cbf.1003","article-title":"Glutamine and glutamate--their central role in cell metabolism and function","volume":"21","author":"Newsholme","year":"2003","journal-title":"Cell Biochem. Funct."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"313","DOI":"10.1038\/onc.2009.358","article-title":"Q\u2019s next: The diverse functions of glutamine in metabolism, cell biology and cancer","volume":"29","author":"DeBerardinis","year":"2010","journal-title":"Oncogene"},{"key":"ref_3","doi-asserted-by":"crossref","unstructured":"Cruzat, V., Macedo Rogero, M., Noel Keane, K., Curi, R., and Newsholme, P. (2018). Glutamine: Metabolism and Immune Function, Supplementation and Clinical Translation. Nutrients, 10.","DOI":"10.20944\/preprints201809.0459.v1"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"749","DOI":"10.1038\/nrc.2016.114","article-title":"From Krebs to clinic: Glutamine metabolism to cancer therapy","volume":"16","author":"Altman","year":"2016","journal-title":"Nat. Rev. Cancer"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"3143","DOI":"10.1016\/j.bbagen.2012.09.008","article-title":"Glutathione synthesis","volume":"1830","author":"Lu","year":"2013","journal-title":"Biochim. Biophys. Acta"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"1811","DOI":"10.15252\/embj.201796697","article-title":"Molecular definitions of autophagy and related processes","volume":"36","author":"Galluzzi","year":"2017","journal-title":"EMBO J."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"421","DOI":"10.1038\/s41580-020-0250-z","article-title":"Mechanisms, regulation and functions of the unfolded protein response","volume":"21","author":"Hetz","year":"2020","journal-title":"Nat. Rev. Mol. Cell Biol."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"1374","DOI":"10.15252\/embr.201642195","article-title":"The integrated stress response","volume":"17","author":"Koryga","year":"2016","journal-title":"EMBO Rep."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"2464986","DOI":"10.1080\/27694127.2025.2464986","article-title":"Autophagy machinery as exploited by viruses","volume":"4","author":"Munz","year":"2025","journal-title":"Autophagy Rep."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"960","DOI":"10.1016\/j.cell.2017.02.004","article-title":"mTOR Signaling in Growth, Metabolism, and Disease","volume":"168","author":"Saxton","year":"2017","journal-title":"Cell"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"609","DOI":"10.1016\/j.virol.2015.02.038","article-title":"Viral activation of cellular metabolism","volume":"479\u2013480","author":"Sanchez","year":"2015","journal-title":"Virology"},{"key":"ref_12","doi-asserted-by":"crossref","unstructured":"Thaker, S.K., Ch\u2019ng, J., and Christofk, H.R. (2019). Viral hijacking of cellular metabolism. BMC Biol., 17.","DOI":"10.1186\/s12915-019-0678-9"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"789","DOI":"10.1016\/j.tim.2015.08.007","article-title":"Stealing the Keys to the Kitchen: Viral Manipulation of the Host Cell Metabolic Network","volume":"23","author":"Goodwin","year":"2015","journal-title":"Trends Microbiol."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"a033001","DOI":"10.1101\/cshperspect.a033001","article-title":"Translational Control in Virus-Infected Cells","volume":"11","author":"Thompson","year":"2019","journal-title":"Cold Spring Harb. Perspect. Biol."},{"key":"ref_15","doi-asserted-by":"crossref","unstructured":"Trinh, Q.D., Takada, K., Pham, N.T.K., Takano, C., Namiki, T., Ito, S., Takeda, Y., Okitsu, S., Ushijima, H., and Hayakawa, S. (2025). Oxidative Stress Enhances Rubella Virus Infection in Immortalized Human First-Trimester Trophoblasts. Int. J. Mol. Sci., 26.","DOI":"10.3390\/ijms26031041"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"450","DOI":"10.1016\/j.virol.2015.03.042","article-title":"Viruses and the autophagy pathway","volume":"479\u2013480","author":"Jackson","year":"2015","journal-title":"Virology"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"437","DOI":"10.1016\/j.cmet.2020.07.007","article-title":"Elevated Glucose Levels Favor SARS-CoV-2 Infection and Monocyte Response through a HIF-1alpha\/Glycolysis-Dependent Axis","volume":"32","author":"Codo","year":"2020","journal-title":"Cell Metab."},{"key":"ref_18","doi-asserted-by":"crossref","unstructured":"Ke, P.Y. (2018). The Multifaceted Roles of Autophagy in Flavivirus-Host Interactions. Int. J. Mol. Sci., 19.","DOI":"10.3390\/ijms19123940"},{"key":"ref_19","doi-asserted-by":"crossref","unstructured":"Trinh, Q.D., Takada, K., Pham, N.T.K., Takano, C., Namiki, T., Ikuta, R., Hayashida, S., Okitsu, S., Ushijima, H., and Komine-Aizawa, S. (2022). Enhancement of Rubella Virus Infection in Immortalized Human First-Trimester Trophoblasts Under Low-Glucose Stress Conditions. Front. Microbiol., 13.","DOI":"10.3389\/fmicb.2022.904189"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"10","DOI":"10.1128\/JVI.02237-16","article-title":"Glycolysis, Glutaminolysis, and Fatty Acid Synthesis Are Required for Distinct Stages of Kaposi\u2019s Sarcoma-Associated Herpesvirus Lytic Replication","volume":"91","author":"Sanchez","year":"2017","journal-title":"J. Virol."},{"key":"ref_21","doi-asserted-by":"crossref","unstructured":"Scalise, M., Pochini, L., Console, L., Losso, M.A., and Indiveri, C. (2018). The Human SLC1A5 (ASCT2) Amino Acid Transporter: From Function to Structure and Role in Cell Biology. Front. Cell Dev. Biol., 6.","DOI":"10.3389\/fcell.2018.00096"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"521","DOI":"10.1016\/j.cell.2008.11.044","article-title":"Bidirectional transport of amino acids regulates mTOR and autophagy","volume":"136","author":"Nicklin","year":"2009","journal-title":"Cell"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"2467","DOI":"10.1093\/jn\/131.9.2467S","article-title":"Mechanisms governing the expression of the enzymes of glutamine metabolism--glutaminase and glutamine synthetase","volume":"131","author":"Labow","year":"2001","journal-title":"J. Nutr."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"163","DOI":"10.1146\/annurev-bioeng-071516-044546","article-title":"Glutaminolysis: A Hallmark of Cancer Metabolism","volume":"19","author":"Yang","year":"2017","journal-title":"Annu. Rev. Biomed. Eng."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"3678","DOI":"10.1172\/JCI69600","article-title":"Glutamine and cancer: Cell biology, physiology, and clinical opportunities","volume":"123","author":"Hensley","year":"2013","journal-title":"J. Clin. Investig."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"27","DOI":"10.1016\/j.cmet.2015.12.006","article-title":"The Emerging Hallmarks of Cancer Metabolism","volume":"23","author":"Pavlova","year":"2016","journal-title":"Cell Metab."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"29","DOI":"10.1016\/S0166-1280(01)00352-9","article-title":"An ab initio exploratory study of side chain conformations for selected backbone conformations of N-acetyl-l-glutamine-N-methylamide","volume":"545","author":"Tarditi","year":"2001","journal-title":"J. Mol. Struct. THEOCHEM"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"a032870","DOI":"10.1101\/cshperspect.a032870","article-title":"Role of eIF2alpha Kinases in Translational Control and Adaptation to Cellular Stress","volume":"10","author":"Wek","year":"2018","journal-title":"Cold Spring Harb. Perspect. Biol."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"133","DOI":"10.1038\/nrm3522","article-title":"Amino acid signalling upstream of mTOR","volume":"14","author":"Jewell","year":"2013","journal-title":"Nat. Rev. Mol. Cell Biol."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"194","DOI":"10.1126\/science.1259472","article-title":"Metabolism. Differential regulation of mTORC1 by leucine and glutamine","volume":"347","author":"Jewell","year":"2015","journal-title":"Science"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"467452","DOI":"10.1155\/2014\/467452","article-title":"RNA Viruses: ROS-Mediated Cell Death","volume":"2014","author":"Reshi","year":"2014","journal-title":"Int. J. Cell Biol."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"7683","DOI":"10.1093\/nar\/gkt563","article-title":"The eIF2alpha\/ATF4 pathway is essential for stress-induced autophagy gene expression","volume":"41","author":"Maurin","year":"2013","journal-title":"Nucleic Acids Res."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"eaat5314","DOI":"10.1126\/science.aat5314","article-title":"The integrated stress response: From mechanism to disease","volume":"368","author":"Walter","year":"2020","journal-title":"Science"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"4418","DOI":"10.1111\/febs.70166","article-title":"Emerging roles for integrated stress response signaling in homeostasis","volume":"292","author":"Nandakumar","year":"2025","journal-title":"FEBS J."},{"key":"ref_35","doi-asserted-by":"crossref","unstructured":"Jeong, J., Kim, J., and Kim, M.S. (2025). Dual Nature of Mitochondrial Integrated Stress Response: Molecular Switches from Protection to Pathology. Genes, 16.","DOI":"10.3390\/genes16080957"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"107151","DOI":"10.1016\/j.jbc.2024.107151","article-title":"The integrated stress response in metabolic adaptation","volume":"300","author":"Ryoo","year":"2024","journal-title":"J. Biol. Chem."},{"key":"ref_37","doi-asserted-by":"crossref","unstructured":"Zhu, J., and Marciniak, S.J. (2026). GCN2 in proteostasis: Structural logic, signalling networks and disease. FEBS J.","DOI":"10.1111\/febs.70480"},{"key":"ref_38","doi-asserted-by":"crossref","unstructured":"Yuan, J.R., Tang, J., and Sheng, R. (2026). The stress responsive transcription factor ATF4: From molecular structure to disease mechanisms. J. Adv. Res.","DOI":"10.1016\/j.jare.2026.03.017"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"24785","DOI":"10.1074\/jbc.M111.232439","article-title":"ICP34.5 protein of herpes simplex virus facilitates the initiation of protein translation by bridging eukaryotic initiation factor 2alpha (eIF2alpha) and protein phosphatase 1","volume":"286","author":"Li","year":"2011","journal-title":"J. Biol. Chem."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"1361","DOI":"10.1038\/s41564-020-0759-0","article-title":"Inhibition of the integrated stress response by viral proteins that block p-eIF2-eIF2B association","volume":"5","author":"Rabouw","year":"2020","journal-title":"Nat. Microbiol."},{"key":"ref_41","doi-asserted-by":"crossref","unstructured":"Adjibade, P., and Mazroui, R. (2026). Regulation of Translation of ATF4 mRNA: A Focus on Translation Initiation Factors and RNA-Binding Proteins. Cells, 15.","DOI":"10.3390\/cells15020188"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"390","DOI":"10.1038\/s41420-025-02683-7","article-title":"The ATF4-glutamine axis: A central node in cancer metabolism, stress adaptation, and therapeutic targeting","volume":"11","author":"Yan","year":"2025","journal-title":"Cell Death Discov."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"2082","DOI":"10.1038\/emboj.2010.81","article-title":"The GCN2-ATF4 pathway is critical for tumour cell survival and proliferation in response to nutrient deprivation","volume":"29","author":"Ye","year":"2010","journal-title":"EMBO J."},{"key":"ref_44","doi-asserted-by":"crossref","unstructured":"Chan, S.W. (2014). Unfolded protein response in hepatitis C virus infection. Front. Microbiol., 5.","DOI":"10.3389\/fmicb.2014.00233"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"169","DOI":"10.1016\/j.molcel.2017.06.017","article-title":"The Unfolded Protein Response and Cell Fate Control","volume":"69","author":"Hetz","year":"2018","journal-title":"Mol. Cell"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"100759","DOI":"10.1016\/j.jbc.2021.100759","article-title":"The chaperone GRP78 is a host auxiliary factor for SARS-CoV-2 and GRP78 depleting antibody blocks viral entry and infection","volume":"296","author":"Carlos","year":"2021","journal-title":"J. Biol. Chem."},{"key":"ref_47","doi-asserted-by":"crossref","unstructured":"Shin, J., Toyoda, S., Fukuhara, A., and Shimomura, I. (2022). GRP78, a Novel Host Factor for SARS-CoV-2: The Emerging Roles in COVID-19 Related to Metabolic Risk Factors. Biomedicines, 10.","DOI":"10.3390\/biomedicines10081995"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"29","DOI":"10.1080\/19768354.2023.2181217","article-title":"Crosstalk between endoplasmic reticulum stress response and autophagy in human diseases","volume":"27","author":"Kwon","year":"2023","journal-title":"Anim. Cells Syst."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"280","DOI":"10.1016\/j.molcel.2010.09.023","article-title":"Autophagy and the integrated stress response","volume":"40","author":"Kroemer","year":"2010","journal-title":"Mol. Cell"},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"349","DOI":"10.1038\/s41580-018-0003-4","article-title":"Mechanism and medical implications of mammalian autophagy","volume":"19","author":"Dikic","year":"2018","journal-title":"Nat. Rev. Mol. Cell Biol."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"2358","DOI":"10.1128\/JVI.02309-14","article-title":"Dengue virus induces and requires glycolysis for optimal replication","volume":"89","author":"Fontaine","year":"2015","journal-title":"J. Virol."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"360","DOI":"10.1016\/j.tim.2011.04.002","article-title":"Viral effects on metabolism: Changes in glucose and glutamine utilization during human cytomegalovirus infection","volume":"19","author":"Yu","year":"2011","journal-title":"Trends Microbiol."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"694","DOI":"10.1016\/j.cmet.2014.03.009","article-title":"Adenovirus E4ORF1-induced MYC activation promotes host cell anabolic glucose metabolism and virus replication","volume":"19","author":"Thai","year":"2014","journal-title":"Cell Metab."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"1640","DOI":"10.1016\/j.celrep.2017.04.039","article-title":"Targeting Metabolic Reprogramming by Influenza Infection for Therapeutic Intervention","volume":"19","author":"Smallwood","year":"2017","journal-title":"Cell Rep."},{"key":"ref_55","doi-asserted-by":"crossref","unstructured":"Wu, Y., Zhang, Z., Li, Y., and Li, Y. (2021). The Regulation of Integrated Stress Response Signaling Pathway on Viral Infection and Viral Antagonism. Front. Microbiol., 12.","DOI":"10.3389\/fmicb.2021.814635"},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"e2511857122","DOI":"10.1073\/pnas.2511857122","article-title":"The integrated stress response suppresses antiviral RNA interference by autophagy-mediated degradation of the RNA-induced silencing complex","volume":"122","author":"Wang","year":"2025","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"e0165625","DOI":"10.1128\/jvi.01656-25","article-title":"Seneca Valley virus 3C protease targets the Nrf2\/HO-1 pathway to antagonize its antiviral activity","volume":"100","author":"Song","year":"2026","journal-title":"J. Virol."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"406","DOI":"10.1007\/s00018-025-05951-y","article-title":"Synergetic contributions of Seneca Valley virus 3 C and 3D proteins to induction of ferroptosis for viral replication","volume":"82","author":"Song","year":"2025","journal-title":"Cell. Mol. Life Sci. CMLS"},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"305","DOI":"10.1042\/CS20201042","article-title":"Host cell glutamine metabolism as a potential antiviral target","volume":"135","author":"Hirabara","year":"2021","journal-title":"Clin. Sci."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"1245","DOI":"10.1038\/s42255-022-00652-3","article-title":"Innate metabolic responses against viral infections","volume":"4","author":"Palmer","year":"2022","journal-title":"Nat. Metab."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"6551","DOI":"10.1038\/s41467-022-34065-3","article-title":"The stress-inducible ER chaperone GRP78\/BiP is upregulated during SARS-CoV-2 infection and acts as a pro-viral protein","volume":"13","author":"Shin","year":"2022","journal-title":"Nat. Commun."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"273","DOI":"10.1016\/j.cell.2017.09.021","article-title":"Ferroptosis: A Regulated Cell Death Nexus Linking Metabolism, Redox Biology, and Disease","volume":"171","author":"Stockwell","year":"2017","journal-title":"Cell"},{"key":"ref_63","doi-asserted-by":"crossref","unstructured":"Wang, J., Zhu, J., Ren, S., Zhang, Z., Niu, K., Li, H., Wu, W., and Peng, C. (2023). The role of ferroptosis in virus infections. Front. Microbiol., 14.","DOI":"10.3389\/fmicb.2023.1279655"},{"key":"ref_64","doi-asserted-by":"crossref","unstructured":"Fung, T.S., and Liu, D.X. (2014). Coronavirus infection, ER stress, apoptosis and innate immunity. Front. Microbiol., 5.","DOI":"10.3389\/fmicb.2014.00296"},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"2723","DOI":"10.1128\/JVI.02050-10","article-title":"West Nile virus differentially modulates the unfolded protein response to facilitate replication and immune evasion","volume":"85","author":"Ambrose","year":"2011","journal-title":"J. Virol."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"2399945","DOI":"10.1080\/22221751.2024.2399945","article-title":"African swine fever virus modulates the endoplasmic reticulum stress-ATF6-calcium axis to facilitate viral replication","volume":"13","author":"Wang","year":"2024","journal-title":"Emerg. Microbes Infect."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"e70187","DOI":"10.1096\/fj.202400931RR","article-title":"EP152R-mediated endoplasmic reticulum stress contributes to African swine fever virus infection via the PERK-eIF2alpha pathway","volume":"38","author":"Liang","year":"2024","journal-title":"FASEB J."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"172","DOI":"10.1186\/s13567-024-01433-4","article-title":"African swine fever virus enhances viral replication by increasing intracellular reduced glutathione levels, which suppresses stress granule formation","volume":"55","author":"Gao","year":"2024","journal-title":"Vet. Res."},{"key":"ref_69","doi-asserted-by":"crossref","unstructured":"Wang, Q., Zhou, L., Wang, J., Su, D., Li, D., Du, Y., Yang, G., Zhang, G., and Chu, B. (2022). African Swine Fever Virus K205R Induces ER Stress and Consequently Activates Autophagy and the NF-kappaB Signaling Pathway. Viruses, 14.","DOI":"10.3390\/v14020394"},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"3455","DOI":"10.1128\/JVI.03453-14","article-title":"Characterization of dengue virus NS4A and NS4B protein interaction","volume":"89","author":"Zou","year":"2015","journal-title":"J. Virol."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"6","DOI":"10.1016\/j.tcb.2015.08.010","article-title":"Ubiquitin-Dependent and Independent Signals in Selective Autophagy","volume":"26","author":"Khaminets","year":"2016","journal-title":"Trends Cell Biol."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"205","DOI":"10.1002\/rmv.687","article-title":"Viruses and the fuel sensor: The emerging link between AMPK and virus replication","volume":"21","author":"Mankouri","year":"2011","journal-title":"Rev. Med. Virol."},{"key":"ref_73","doi-asserted-by":"crossref","unstructured":"Mayer, K.A., Stockl, J., Zlabinger, G.J., and Gualdoni, G.A. (2019). Hijacking the Supplies: Metabolism as a Novel Facet of Virus-Host Interaction. Front. Immunol., 10.","DOI":"10.3389\/fimmu.2019.01533"},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"9369","DOI":"10.1128\/JVI.05102-11","article-title":"Human cytomegalovirus infection maintains mTOR activity and its perinuclear localization during amino acid deprivation","volume":"85","author":"Clippinger","year":"2011","journal-title":"J. Virol."},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"253","DOI":"10.1016\/j.chom.2008.03.002","article-title":"Human cytomegalovirus protein UL38 inhibits host cell stress responses by antagonizing the tuberous sclerosis protein complex","volume":"3","author":"Moorman","year":"2008","journal-title":"Cell Host Microbe"},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"149","DOI":"10.1016\/bs.aivir.2016.02.002","article-title":"Autophagy and Mammalian Viruses: Roles in Immune Response, Viral Replication, and Beyond","volume":"95","author":"Paul","year":"2016","journal-title":"Adv. Virus Res."},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"132","DOI":"10.1038\/ncb2152","article-title":"AMPK and mTOR regulate autophagy through direct phosphorylation of Ulk1","volume":"13","author":"Kim","year":"2011","journal-title":"Nat. Cell Biol."},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"722","DOI":"10.1038\/nri3532","article-title":"Autophagy in infection, inflammation and immunity","volume":"13","author":"Deretic","year":"2013","journal-title":"Nat. Rev. Immunol."},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"22147","DOI":"10.1074\/jbc.M110.192500","article-title":"Flavivirus NS4A-induced autophagy protects cells against death and enhances virus replication","volume":"286","author":"McLean","year":"2011","journal-title":"J. Biol. Chem."},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"001773","DOI":"10.1099\/jgv.0.001773","article-title":"Membrane architects: How positive-strand RNA viruses restructure the cell","volume":"103","author":"Neufeldt","year":"2022","journal-title":"J. Gen. Virol."},{"key":"ref_81","doi-asserted-by":"crossref","unstructured":"Zhai, H., Wang, T., Liu, D., Pan, L., Sun, Y., and Qiu, H.J. (2023). Autophagy as a dual-faced host response to viral infections. Front. Cell. Infect. Microbiol., 13.","DOI":"10.3389\/fcimb.2023.1289170"},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"e2127","DOI":"10.1038\/cddis.2015.409","article-title":"Dengue-induced autophagy, virus replication and protection from cell death require ER stress (PERK) pathway activation","volume":"7","author":"Datan","year":"2016","journal-title":"Cell Death Dis."},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"422","DOI":"10.1016\/j.chom.2010.10.006","article-title":"Dengue virus-induced autophagy regulates lipid metabolism","volume":"8","author":"Heaton","year":"2010","journal-title":"Cell Host Microbe"},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"301","DOI":"10.1016\/j.virol.2013.06.026","article-title":"Glycolytic control of vacuolar-type ATPase activity: A mechanism to regulate influenza viral infection","volume":"444","author":"Kohio","year":"2013","journal-title":"Virology"},{"key":"ref_85","doi-asserted-by":"crossref","unstructured":"Ritter, J.B., Wahl, A.S., Freund, S., Genzel, Y., and Reichl, U. (2010). Metabolic effects of influenza virus infection in cultured animal cells: Intra- and extracellular metabolite profiling. BMC Syst. Biol., 4.","DOI":"10.1186\/1752-0509-4-61"},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"1641","DOI":"10.1080\/07391102.2023.2292307","article-title":"Investigation of the mutated antimicrobial peptides to inhibit ACE2, TMPRSS2 and GRP78 receptors of SARS-CoV-2 and angiotensin II type 1 receptor (AT1R) as well as controlling COVID-19 disease","volume":"43","author":"Balmeh","year":"2025","journal-title":"J. Biomol. Struct. Dyn."},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"108289","DOI":"10.1016\/j.micpath.2026.108289","article-title":"Hepatitis B virus induces T cell exhaustion by increasing mitochondrial ROS accumulation","volume":"212","author":"Cheng","year":"2026","journal-title":"Microb. Pathog."},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"106323","DOI":"10.1016\/j.antiviral.2025.106323","article-title":"Isochlorogenic acid A impairs hepatitis B virus replication by interference with various steps of hepatitis B virus life cycle involving HO-1-mediated ROS modulation","volume":"245","author":"Koyaweda","year":"2026","journal-title":"Antivir. Res."},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"548","DOI":"10.1080\/15548627.2019.1632104","article-title":"Glucosamine promotes hepatitis B virus replication through its dual effects in suppressing autophagic degradation and inhibiting MTORC1 signaling","volume":"16","author":"Lin","year":"2020","journal-title":"Autophagy"},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"64","DOI":"10.1016\/j.jhep.2020.12.034","article-title":"Hypoxia inducible factors regulate hepatitis B virus replication by activating the basal core promoter","volume":"75","author":"Wing","year":"2021","journal-title":"J. Hepatol."},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"789","DOI":"10.1002\/hep.28949","article-title":"Hepatitis C virus infection triggers a tumor-like glutamine metabolism","volume":"65","author":"Levy","year":"2017","journal-title":"Hepatology"},{"key":"ref_92","doi-asserted-by":"crossref","unstructured":"Ke, P.Y., and Yeh, C.T. (2024). Functional Role of Hepatitis C Virus NS5A in the Regulation of Autophagy. Pathogens, 13.","DOI":"10.3390\/pathogens13110980"},{"key":"ref_93","doi-asserted-by":"crossref","unstructured":"Lee, J., and Ou, J.J. (2024). HCV-induced autophagy and innate immunity. Front. Immunol., 15.","DOI":"10.3389\/fimmu.2024.1305157"},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"199285","DOI":"10.1016\/j.virusres.2023.199285","article-title":"Oxidative stress enhances rotavirus oncolysis in breast cancer and leukemia, except in melanoma with abundant matrix","volume":"339","author":"Guerrero","year":"2024","journal-title":"Virus Res."},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"186","DOI":"10.1016\/j.ijbiomac.2022.12.219","article-title":"Sodium butyrate protects against rotavirus-induced intestinal epithelial barrier damage by activating AMPK-Nrf2 signaling pathway in IPEC-J2 cells","volume":"228","author":"Dong","year":"2023","journal-title":"Int. J. Biol. Macromol."},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"69","DOI":"10.1186\/s40104-021-00592-0","article-title":"Protective effects of sodium butyrate on rotavirus inducing endoplasmic reticulum stress-mediated apoptosis via PERK-eIF2alpha signaling pathway in IPEC-J2 cells","volume":"12","author":"Zhao","year":"2021","journal-title":"J. Anim. Sci. Biotechnol."},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"38","DOI":"10.5501\/wjv.v5.i2.38","article-title":"Inflammatory and oxidative stress in rotavirus infection","volume":"5","author":"Guerrero","year":"2016","journal-title":"World J. Virol."},{"key":"ref_98","doi-asserted-by":"crossref","first-page":"110485","DOI":"10.1016\/j.virol.2025.110485","article-title":"Critical role of ferroptosis in viral infection and host responses","volume":"606","author":"Mao","year":"2025","journal-title":"Virology"}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/27\/11\/4717\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,5,25]],"date-time":"2026-05-25T01:49:19Z","timestamp":1779673759000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/27\/11\/4717"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,5,23]]},"references-count":98,"journal-issue":{"issue":"11","published-online":{"date-parts":[[2026,6]]}},"alternative-id":["ijms27114717"],"URL":"https:\/\/doi.org\/10.3390\/ijms27114717","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,5,23]]}}}