{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,3]],"date-time":"2026-08-03T23:51:19Z","timestamp":1785801079564,"version":"3.56.0"},"reference-count":102,"publisher":"MDPI AG","issue":"11","license":[{"start":{"date-parts":[[2021,11,8]],"date-time":"2021-11-08T00:00:00Z","timestamp":1636329600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100004488","name":"Croatian Science Foundation","doi-asserted-by":"publisher","award":["IP-2016-06-8027"],"award-info":[{"award-number":["IP-2016-06-8027"]}],"id":[{"id":"10.13039\/501100004488","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004488","name":"Croatian Science Foundation","doi-asserted-by":"publisher","award":["IP-CORONA-2020-04-2045"],"award-info":[{"award-number":["IP-CORONA-2020-04-2045"]}],"id":[{"id":"10.13039\/501100004488","id-type":"DOI","asserted-by":"publisher"}]},{"name":"University of Rijeka","award":["19-41-1551"],"award-info":[{"award-number":["19-41-1551"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Viruses"],"abstract":"<jats:p>Sickness behavior is the common denominator for a plethora of changes in normal behavioral routines and systemic metabolism during an infection. Typical symptoms include temperature, muscle weakness, and loss of appetite. Whereas we experience these changes as a pathology, in fact they are a carefully orchestrated response mediated by the immune system. Its purpose is to optimize immune cell functionality against pathogens whilst minimizing viral replication in infected cells. Sickness behavior is controlled at several levels, most notably by the central nervous system, but also by other organs that mediate systemic homeostasis, such as the liver and adipose tissue. Nevertheless, the changes mediated by these organs are ultimately initiated by immune cells, usually through local or systemic secretion of cytokines. The nature of infection determines which cytokine profile is induced by immune cells and therefore which sickness behavior ensues. In context of infection, sickness behavior is typically beneficial. However, inappropriate activation of the immune system may induce adverse aspects of sickness behavior. For example, tissue stress caused by obesity may result in chronic activation of the immune system, leading to lasting changes in systemic metabolism. Concurrently, metabolic disease prevents induction of appropriate sickness behavior following viral infection, thus impairing the normal immune response. In this article, we will revisit recent literature that elucidates both the benefits and the negative aspects of sickness behavior in context of viral infection.<\/jats:p>","DOI":"10.3390\/v13112245","type":"journal-article","created":{"date-parts":[[2021,11,8]],"date-time":"2021-11-08T22:08:41Z","timestamp":1636409321000},"page":"2245","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":37,"title":["Immunological Mechanisms of Sickness Behavior in Viral Infection"],"prefix":"10.3390","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4133-7000","authenticated-orcid":false,"given":"Mia","family":"Krapi\u0107","sequence":"first","affiliation":[{"name":"Department of Histology and Embryology, Faculty of Medicine, University of Rijeka, 51000 Rijeka, Croatia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Inga","family":"Kavazovi\u0107","sequence":"additional","affiliation":[{"name":"Department of Histology and Embryology, Faculty of Medicine, University of Rijeka, 51000 Rijeka, Croatia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1333-8882","authenticated-orcid":false,"given":"Felix M.","family":"Wensveen","sequence":"additional","affiliation":[{"name":"Department of Histology and Embryology, Faculty of Medicine, University of Rijeka, 51000 Rijeka, Croatia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,11,8]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"154","DOI":"10.1016\/S0166-2236(00)02088-9","article-title":"Cytokine-induced sickness behaviour: Mechanisms and implications","volume":"25","author":"Konsman","year":"2002","journal-title":"Trends Neurosci."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"164","DOI":"10.1016\/j.immuni.2018.05.005","article-title":"Virus-Induced Interferon-\u03b3 Causes Insulin Resistance in Skeletal Muscle and Derails Glycemic Control in Obesity","volume":"49","author":"Wueest","year":"2018","journal-title":"Immunity"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"376","DOI":"10.1038\/ni.3120","article-title":"NK cells link obesity-induced adipose stress to inflammation and insulin resistance","volume":"16","author":"Wensveen","year":"2015","journal-title":"Nat. Immunol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"322","DOI":"10.1016\/j.smim.2015.10.006","article-title":"Interactions between adipose tissue and the immune system in health and malnutrition","volume":"27","author":"Wensveen","year":"2015","journal-title":"Semin. Immunol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"982","DOI":"10.1002\/eji.201847895","article-title":"\u2018Beauty and the beast\u2019 in infection: How immune-endocrine interactions regulate systemic metabolism in the context of infection","volume":"49","author":"Wensveen","year":"2019","journal-title":"Eur. J. Immunol."},{"key":"ref_6","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_7","doi-asserted-by":"crossref","first-page":"1176","DOI":"10.1099\/mic.0.034744-0","article-title":"Glucose and glucose 6-phosphate as carbon sources in extra- and intracellular growth of enteroinvasive Escherichia coli and Salmonella enterica","volume":"156","author":"Gotz","year":"2010","journal-title":"Microbiology"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"553","DOI":"10.1038\/nri.2016.70","article-title":"A guide to immunometabolism for immunologists","volume":"16","author":"Kishton","year":"2016","journal-title":"Nat. Rev. Immunol."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"121","DOI":"10.1042\/bj2390121","article-title":"Metabolism of glucose, glutamine, long-chain fatty acids and ketone bodies by murine macrophages","volume":"239","author":"Newsholme","year":"1986","journal-title":"Biochem. J."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"331","DOI":"10.1038\/s41590-020-0598-4","article-title":"Germinal center B cells selectively oxidize fatty acids for energy while conducting minimal glycolysis","volume":"21","author":"Weisel","year":"2020","journal-title":"Nat. Immunol."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"881","DOI":"10.1038\/nature05488","article-title":"Abdominal obesity and metabolic syndrome","volume":"444","author":"Despres","year":"2006","journal-title":"Nature"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"108637","DOI":"10.1016\/j.diabres.2020.108637","article-title":"Type 2 diabetes and viral infection; cause and effect of disease","volume":"172","author":"Gasparini","year":"2021","journal-title":"Diabetes Res. Clin. Pract."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"e3319","DOI":"10.1002\/dmrr.3319","article-title":"Diabetes is a risk factor for the progression and prognosis of COVID-19","volume":"36","author":"Guo","year":"2020","journal-title":"Diabetes Metab. Res. Rev."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"829","DOI":"10.1056\/NEJMoa1008862","article-title":"Diabetes mellitus, fasting glucose, and risk of cause-specific death","volume":"364","author":"Kaptoge","year":"2011","journal-title":"N. Engl. J. Med."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"774","DOI":"10.1038\/s42255-021-00407-6","article-title":"Acute and long-term disruption of glycometabolic control after SARS-CoV-2 infection","volume":"3","author":"Montefusco","year":"2021","journal-title":"Nat. Metab."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"441","DOI":"10.3389\/fimmu.2018.00441","article-title":"NKG2D: A Master Regulator of Immune Cell Responsiveness","volume":"9","author":"Wensveen","year":"2018","journal-title":"Front. Immunol."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"1289","DOI":"10.1017\/S0033291704001953","article-title":"Production of pro-inflammatory cytokines correlates with the symptoms of acute sickness behaviour in humans","volume":"34","author":"Fazou","year":"2004","journal-title":"Psychol. Med."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"87","DOI":"10.1017\/S1466252308001448","article-title":"Sickness behavior, its mechanisms and significance","volume":"9","author":"Tizard","year":"2008","journal-title":"Anim. Health Res. Rev."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"2573","DOI":"10.1523\/JNEUROSCI.2887-19.2020","article-title":"EP3R-Expressing Glutamatergic Preoptic Neurons Mediate Inflammatory Fever","volume":"40","author":"Machado","year":"2020","journal-title":"J. Neurosci."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"335","DOI":"10.1038\/nri3843","article-title":"Fever and the thermal regulation of immunity: The immune system feels the heat","volume":"15","author":"Evans","year":"2015","journal-title":"Nat. Rev. Immunol."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"38","DOI":"10.1016\/j.imlet.2018.10.006","article-title":"Pyrogens, a polypeptide produces fever by metabolic changes in hypothalamus: Mechanisms and detections","volume":"204","author":"Prajitha","year":"2018","journal-title":"Immunol. Lett."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"469","DOI":"10.1016\/S0025-6196(12)60394-2","article-title":"Thermoregulation and fever in normal persons and in those with spinal cord injuries","volume":"67","author":"Schmidt","year":"1992","journal-title":"Mayo Clin. Proc."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"137","DOI":"10.1016\/j.immuni.2018.11.013","article-title":"Fever Promotes T Lymphocyte Trafficking via a Thermal Sensory Pathway Involving Heat Shock Protein 90 and alpha4 Integrins","volume":"50","author":"Lin","year":"2019","journal-title":"Immunity"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"22357","DOI":"10.1073\/pnas.1922683117","article-title":"Febrile temperature change modulates CD4 T cell differentiation via a TRPV channel-regulated Notch-dependent pathway","volume":"117","author":"Umar","year":"2020","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_25","doi-asserted-by":"crossref","unstructured":"Townsend, L., Dyer, A.H., Jones, K., Dunne, J., Mooney, A., Gaffney, F., O\u2019Connor, L., Leavy, D., O\u2019Brien, K., and Dowds, J. (2020). Persistent fatigue following SARS-CoV-2 infection is common and independent of severity of initial infection. PLoS ONE, 15.","DOI":"10.1371\/journal.pone.0240784"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"1009","DOI":"10.1093\/rheumatology\/keq454","article-title":"Biological mechanisms of chronic fatigue","volume":"50","author":"Norheim","year":"2011","journal-title":"Rheumatology"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"643","DOI":"10.1016\/S0893-133X(01)00407-9","article-title":"Neurobehavioral effects of interferon-alpha in cancer patients: Phenomenology and paroxetine responsiveness of symptom dimensions","volume":"26","author":"Capuron","year":"2002","journal-title":"Neuropsychopharmacology"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"1081","DOI":"10.1056\/NEJM196911132812001","article-title":"Serum lipids in infection","volume":"281","author":"Gallin","year":"1969","journal-title":"N. Engl. J. Med."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"1169","DOI":"10.1194\/jlr.R300019-JLR200","article-title":"Effects of infection and inflammation on lipid and lipoprotein metabolism: Mechanisms and consequences to the host","volume":"45","author":"Khovidhunkit","year":"2004","journal-title":"J. Lipid Res."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"2096","DOI":"10.1111\/bph.15189","article-title":"Brain control of appetite during sickness","volume":"178","author":"Aviello","year":"2021","journal-title":"Br. J. Pharmacol."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"5170","DOI":"10.1523\/JNEUROSCI.3919-15.2016","article-title":"The Proinflammatory Cytokine Interleukin 18 Regulates Feeding by Acting on the Bed Nucleus of the Stria Terminalis","volume":"36","author":"Francesconi","year":"2016","journal-title":"J. Neurosci."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"2152","DOI":"10.1172\/JCI118653","article-title":"Endotoxin and cytokines induce expression of leptin, the ob gene product, in hamsters","volume":"97","author":"Grunfeld","year":"1996","journal-title":"J. Clin. Investig."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"1055","DOI":"10.3389\/fimmu.2018.01055","article-title":"Changes in Nutritional Status Impact Immune Cell Metabolism and Function","volume":"9","author":"Alwarawrah","year":"2018","journal-title":"Front. Immunol."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"2446","DOI":"10.1002\/eji.201545502","article-title":"The \u201cBig Bang\u201d in obese fat: Events initiating obesity-induced adipose tissue inflammation","volume":"45","author":"Wensveen","year":"2015","journal-title":"Eur. J. Immunol."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"7062","DOI":"10.1074\/jbc.M007894200","article-title":"Interferon-gamma-induced regulation of peroxisome proliferator-activated receptor gamma and STATs in adipocytes","volume":"276","author":"Waite","year":"2001","journal-title":"J. Biol. Chem."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"E1112","DOI":"10.1152\/ajpendo.00370.2010","article-title":"Both type I and II IFN induce insulin resistance by inducing different isoforms of SOCS expression in 3T3-L1 adipocytes","volume":"300","author":"Wada","year":"2011","journal-title":"Am. J. Physiol. Endocrinol. Metab."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"2776","DOI":"10.1210\/endo.138.7.5242","article-title":"TNF alpha-mediated inhibition and reversal of adipocyte differentiation is accompanied by suppressed expression of PPARgamma without effects on Pref-1 expression","volume":"138","author":"Xing","year":"1997","journal-title":"Endocrinology"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"31936","DOI":"10.1074\/jbc.M109.061655","article-title":"Interferon gamma attenuates insulin signaling, lipid storage, and differentiation in human adipocytes via activation of the JAK\/STAT pathway","volume":"284","author":"McGillicuddy","year":"2009","journal-title":"J. Biol. Chem."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"241","DOI":"10.1210\/en.2006-0692","article-title":"Interleukin-1beta-induced insulin resistance in adipocytes through down-regulation of insulin receptor substrate-1 expression","volume":"148","author":"Jager","year":"2007","journal-title":"Endocrinology"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"677","DOI":"10.1016\/j.imbio.2018.07.014","article-title":"Interleukin 4 affects lipid metabolism and the expression of pro-inflammatory factors in mature rat adipocytes","volume":"223","author":"Szczepankiewicz","year":"2018","journal-title":"Immunobiology"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"385","DOI":"10.1194\/jlr.M041392","article-title":"Interleukin-4 regulates lipid metabolism by inhibiting adipogenesis and promoting lipolysis","volume":"55","author":"Tsao","year":"2014","journal-title":"J. Lipid Res."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"701","DOI":"10.1038\/s41590-019-0397-y","article-title":"CD8(+) T cells induce cachexia during chronic viral infection","volume":"20","author":"Baazim","year":"2019","journal-title":"Nat. Immunol."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"177","DOI":"10.1002\/cphy.c130024","article-title":"Energy metabolism in the liver","volume":"4","author":"Rui","year":"2014","journal-title":"Compr. Physiol."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"257","DOI":"10.1002\/(SICI)1096-9896(199703)181:3<257::AID-PATH756>3.0.CO;2-U","article-title":"Cytokines and the hepatic acute phase response","volume":"181","author":"Moshage","year":"1997","journal-title":"J. Pathol."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"301","DOI":"10.1038\/cmi.2015.97","article-title":"Hepatocytes: A key cell type for innate immunity","volume":"13","author":"Zhou","year":"2016","journal-title":"Cell Mol. Immunol."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"10879","DOI":"10.1038\/s41598-020-67879-6","article-title":"Influenza virus infection affects insulin signaling, fatty acid-metabolizing enzyme expressions, and the tricarboxylic acid cycle in mice","volume":"10","author":"Ohno","year":"2020","journal-title":"Sci. Rep."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"2541","DOI":"10.3389\/fmicb.2019.02541","article-title":"Insulin-Like Growth Factor 1 Regulates Acute Inflammatory Lung Injury Mediated by Influenza Virus Infection","volume":"10","author":"Li","year":"2019","journal-title":"Front. Microbiol."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"848","DOI":"10.1016\/j.dci.2009.02.001","article-title":"Transferrin and ferritin response to bacterial infection: The role of the liver and brain in fish","volume":"33","author":"Neves","year":"2009","journal-title":"Dev. Comp. Immunol."},{"key":"ref_49","first-page":"695","article-title":"Iron Overload in Patients with Chronic Liver Disease","volume":"12","author":"Kowdley","year":"2016","journal-title":"Gastroenterol. Hepatol."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"1267","DOI":"10.3748\/wjg.v27.i13.1267","article-title":"Metabolic complications of hepatitis C virus infection","volume":"27","author":"Chaudhari","year":"2021","journal-title":"World J. Gastroenterol."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"2123","DOI":"10.1038\/s41467-019-10015-4","article-title":"Competition for nutrients and its role in controlling immune responses","volume":"10","author":"Finlay","year":"2019","journal-title":"Nat. Commun."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"771","DOI":"10.1038\/cr.2015.68","article-title":"Metabolic reprogramming in macrophages and dendritic cells in innate immunity","volume":"25","author":"Kelly","year":"2015","journal-title":"Cell Res."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"1345","DOI":"10.1084\/jem.20151159","article-title":"T cell metabolism drives immunity","volume":"212","author":"Buck","year":"2015","journal-title":"J. Exp. Med."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"546","DOI":"10.1002\/ajhb.21045","article-title":"Toward quantifying the usage costs of human immunity: Altered metabolic rates and hormone levels during acute immune activation in men","volume":"22","author":"Muehlenbein","year":"2010","journal-title":"Am. J. Hum. Biol."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"543","DOI":"10.1111\/j.1365-2796.2010.02218.x","article-title":"Energy regulation and neuroendocrine-immune control in chronic inflammatory diseases","volume":"267","author":"Straub","year":"2010","journal-title":"J. Intern. Med."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"1037","DOI":"10.4049\/jimmunol.0903586","article-title":"Glutamine uptake and metabolism are coordinately regulated by ERK\/MAPK during T lymphocyte activation","volume":"185","author":"Carr","year":"2010","journal-title":"J. Immunol."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"2438","DOI":"10.1002\/eji.200838289","article-title":"Glucose deprivation inhibits multiple key gene expression events and effector functions in CD8+ T cells","volume":"38","author":"Cham","year":"2008","journal-title":"Eur. J. Immunol."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"4476","DOI":"10.4049\/jimmunol.180.7.4476","article-title":"Glucose uptake is limiting in T cell activation and requires CD28-mediated Akt-dependent and independent pathways","volume":"180","author":"Jacobs","year":"2008","journal-title":"J. Immunol."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"190","DOI":"10.1016\/j.immuni.2007.07.009","article-title":"Germinal-center organization and cellular dynamics","volume":"27","author":"Allen","year":"2007","journal-title":"Immunity"},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"99","DOI":"10.1016\/j.isci.2018.07.005","article-title":"Initial B Cell Activation Induces Metabolic Reprogramming and Mitochondrial Remodeling","volume":"5","author":"Waters","year":"2018","journal-title":"iScience"},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"979","DOI":"10.1016\/j.tcb.2020.09.006","article-title":"Lipid Metabolism in Regulation of Macrophage Functions","volume":"30","author":"Yan","year":"2020","journal-title":"Trends Cell Biol."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"683","DOI":"10.1016\/S1097-2765(00)00066-6","article-title":"In the absence of extrinsic signals, nutrient utilization by lymphocytes is insufficient to maintain either cell size or viability","volume":"6","author":"Rathmell","year":"2000","journal-title":"Mol. Cell."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"C1560","DOI":"10.1152\/ajpcell.00506.2009","article-title":"Interleukin-7 mediates glucose utilization in lymphocytes through transcriptional regulation of the hexokinase II gene","volume":"298","author":"Chehtane","year":"2010","journal-title":"Am. J. Physiol. Cell Physiol."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"4742","DOI":"10.1182\/blood-2009-10-249540","article-title":"Toll-like receptor-induced changes in glycolytic metabolism regulate dendritic cell activation","volume":"115","author":"Krawczyk","year":"2010","journal-title":"Blood"},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"95","DOI":"10.3389\/fcimb.2019.00095","article-title":"Virus Control of Cell Metabolism for Replication and Evasion of Host Immune Responses","volume":"9","author":"Kolstoe","year":"2019","journal-title":"Front. Cell Infect. Microbiol."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"368","DOI":"10.1016\/j.tim.2011.03.007","article-title":"Multifaceted roles for lipids in viral infection","volume":"19","author":"Heaton","year":"2011","journal-title":"Trends Microbiol."},{"key":"ref_67","doi-asserted-by":"crossref","unstructured":"Vastag, L., Koyuncu, E., Grady, S.L., Shenk, T.E., and Rabinowitz, J.D. (2011). Divergent effects of human cytomegalovirus and herpes simplex virus-1 on cellular metabolism. PLoS Pathog., 7.","DOI":"10.1371\/journal.ppat.1002124"},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"8873","DOI":"10.1038\/ncomms9873","article-title":"MYC-induced reprogramming of glutamine catabolism supports optimal virus replication","volume":"6","author":"Thai","year":"2015","journal-title":"Nat. Commun."},{"key":"ref_69","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_70","doi-asserted-by":"crossref","first-page":"1179","DOI":"10.1038\/nbt.1500","article-title":"Systems-level metabolic flux profiling identifies fatty acid synthesis as a target for antiviral therapy","volume":"26","author":"Munger","year":"2008","journal-title":"Nat. Biotechnol."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"1074","DOI":"10.1016\/j.immuni.2019.10.014","article-title":"Type I Interferon Signaling Disrupts the Hepatic Urea Cycle and Alters Systemic Metabolism to Suppress T Cell Function","volume":"51","author":"Lercher","year":"2019","journal-title":"Immunity"},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"11289","DOI":"10.1038\/s41598-017-10637-y","article-title":"The lipid-sensor TREM2 aggravates disease in a model of LCMV-induced hepatitis","volume":"7","author":"Kosack","year":"2017","journal-title":"Sci. Rep."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"39","DOI":"10.1099\/0022-1317-73-1-39","article-title":"Alterations in antioxidant defences in lung and liver of mice infected with influenza A virus","volume":"73","author":"Hennet","year":"1992","journal-title":"J. Gen. Virol."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"3329","DOI":"10.1016\/j.bbagen.2012.10.012","article-title":"Glutathione and infection","volume":"1830","author":"Morris","year":"2013","journal-title":"Biochim. Biophys. Acta"},{"key":"ref_75","doi-asserted-by":"crossref","unstructured":"Wang, J., Chen, Y., Gao, N., Wang, Y., Tian, Y., Wu, J., Zhang, J., Zhu, J., Fan, D., and An, J. (2013). Inhibitory effect of glutathione on oxidative liver injury induced by dengue virus serotype 2 infections in mice. PLoS ONE, 8.","DOI":"10.1371\/journal.pone.0055407"},{"key":"ref_76","first-page":"512","article-title":"The role of diabetes mellitus in patients with bloodstream infections","volume":"138","author":"Stoeckle","year":"2008","journal-title":"Swiss Med. Wkly."},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"281","DOI":"10.1086\/431587","article-title":"Increased risk of common infections in patients with type 1 and type 2 diabetes mellitus","volume":"41","author":"Muller","year":"2005","journal-title":"Clin. Infect. Dis."},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"617","DOI":"10.1016\/j.idc.2007.07.003","article-title":"Infections in diabetes mellitus and hyperglycemia","volume":"21","author":"Gupta","year":"2007","journal-title":"Infect. Dis. Clin. N. Am."},{"key":"ref_79","doi-asserted-by":"crossref","unstructured":"Jeon, C.Y., and Murray, M.B. (2008). Diabetes mellitus increases the risk of active tuberculosis: A systematic review of 13 observational studies. PLoS Med., 5.","DOI":"10.1371\/journal.pmed.0050181"},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"91","DOI":"10.1016\/j.ijid.2020.03.017","article-title":"Prevalence of comorbidities in the novel Wuhan coronavirus (COVID-19) infection: A systematic review and meta-analysis","volume":"94","author":"Yang","year":"2020","journal-title":"Int. J. Infect. Dis."},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"253","DOI":"10.1016\/bs.vh.2021.06.009","article-title":"Blood glucose regulation in context of infection","volume":"117","author":"Wensveen","year":"2021","journal-title":"Vitam. Horm."},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"923","DOI":"10.3390\/jcm3030923","article-title":"Importance of Beta Cell Function for the Treatment of Type 2 Diabetes","volume":"3","author":"Saisho","year":"2014","journal-title":"J. Clin. Med."},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"19","DOI":"10.1089\/met.2010.0037","article-title":"Association between plasma leptin levels and diabetes mellitus","volume":"9","author":"Bandaru","year":"2011","journal-title":"Metab. Syndr. Relat. Disord."},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"1541","DOI":"10.2337\/dc08-0138","article-title":"Diabetes, glycemic control, and risk of hospitalization with pneumonia: A population-based case-control study","volume":"31","author":"Kornum","year":"2008","journal-title":"Diabetes Care"},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"e000067","DOI":"10.1136\/bmjdrc-2014-000067","article-title":"Bacterial infections in patients with type 1 diabetes: A 14-year follow-up study","volume":"3","author":"Simonsen","year":"2015","journal-title":"BMJ Open Diabetes Res. Care"},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"6196532","DOI":"10.1155\/2019\/6196532","article-title":"Immunol.ogical Impacts of Diabetes on the Susceptibility of Mycobacterium tuberculosis","volume":"2019","author":"Ayelign","year":"2019","journal-title":"J. Immunol. Res."},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"1512","DOI":"10.1016\/j.cell.2016.07.026","article-title":"Opposing Effects of Fasting Metabolism on Tissue Tolerance in Bacterial and Viral Inflammation","volume":"166","author":"Wang","year":"2016","journal-title":"Cell"},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"115","DOI":"10.1038\/nature24057","article-title":"Glucose feeds the TCA cycle via circulating lactate","volume":"551","author":"Hui","year":"2017","journal-title":"Nature"},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"176","DOI":"10.1016\/j.cell.2019.05.003","article-title":"Lactate Is a Natural Suppressor of RLR Signaling by Targeting MAVS","volume":"178","author":"Zhang","year":"2019","journal-title":"Cell"},{"key":"ref_90","first-page":"348","article-title":"Plasma lactate concentration in obesity and type 2 diabetes","volume":"19","author":"Chen","year":"1993","journal-title":"Diabete. Metab."},{"key":"ref_91","first-page":"S39","article-title":"Comprehensive medical evaluation and assessment of comorbidities: Standards of Medical Care in Diabetes-2020","volume":"43","year":"2020","journal-title":"Diabetes Care"},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"141","DOI":"10.1016\/j.diabres.2014.04.006","article-title":"Inflammation as a link between obesity, metabolic syndrome and type 2 diabetes","volume":"105","author":"Esser","year":"2014","journal-title":"Diabetes Res Clin. Pract."},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"1058","DOI":"10.2337\/dc05-2068","article-title":"Burden of infection and insulin resistance in healthy middle-aged men","volume":"29","author":"Vendrell","year":"2006","journal-title":"Diabetes Care"},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"391250","DOI":"10.1155\/2014\/391250","article-title":"Helicobacter pylori infection and insulin resistance in diabetic and nondiabetic population","volume":"2014","author":"Vafaeimanesh","year":"2014","journal-title":"Sci. World J."},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"769","DOI":"10.1016\/S1074-7613(02)00323-0","article-title":"The CD28 signaling pathway regulates glucose metabolism","volume":"16","author":"Frauwirth","year":"2002","journal-title":"Immunity"},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"2133","DOI":"10.1152\/physrev.00063.2017","article-title":"Mechanisms of Insulin Action and Insulin Resistance","volume":"98","author":"Petersen","year":"2018","journal-title":"Physiol. Rev."},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"922","DOI":"10.1016\/j.cmet.2018.08.003","article-title":"Insulin Receptor-Mediated Stimulation Boosts T Cell Immunity during Inflammation and Infection","volume":"28","author":"Tsai","year":"2018","journal-title":"Cell Metab."},{"key":"ref_98","doi-asserted-by":"crossref","first-page":"2279","DOI":"10.1016\/S0140-6736(12)60283-9","article-title":"Prediabetes: A high-risk state for diabetes development","volume":"379","author":"Tabak","year":"2012","journal-title":"Lancet"},{"key":"ref_99","doi-asserted-by":"crossref","first-page":"815","DOI":"10.4093\/dmj.2018.0167","article-title":"Impact of Cytomegalovirus Disease on New-Onset Type 2 Diabetes Mellitus: Population-Based Matched Case-Control Cohort Study","volume":"43","author":"Yoo","year":"2019","journal-title":"Diabetes Metab. J."},{"key":"ref_100","doi-asserted-by":"crossref","first-page":"862","DOI":"10.1016\/j.jhep.2011.11.009","article-title":"Insulin resistance is associated with a higher risk of hepatocellular carcinoma in cirrhotic HIV\/HCV-co-infected patients: Results from ANRS CO13 HEPAVIH","volume":"56","author":"Salmon","year":"2012","journal-title":"J. Hepatol."},{"key":"ref_101","doi-asserted-by":"crossref","first-page":"2863","DOI":"10.2337\/db07-1023","article-title":"Viral trigger for type 1 diabetes: Pros and cons","volume":"57","author":"Filippi","year":"2008","journal-title":"Diabetes"},{"key":"ref_102","doi-asserted-by":"crossref","first-page":"149","DOI":"10.1038\/s42255-021-00347-1","article-title":"SARS-CoV-2 infects and replicates in cells of the human endocrine and exocrine pancreas","volume":"3","author":"Muller","year":"2021","journal-title":"Nat. Metab."}],"container-title":["Viruses"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1999-4915\/13\/11\/2245\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T07:27:46Z","timestamp":1760167666000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1999-4915\/13\/11\/2245"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,11,8]]},"references-count":102,"journal-issue":{"issue":"11","published-online":{"date-parts":[[2021,11]]}},"alternative-id":["v13112245"],"URL":"https:\/\/doi.org\/10.3390\/v13112245","relation":{},"ISSN":["1999-4915"],"issn-type":[{"value":"1999-4915","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,11,8]]}}}