Proc Natl Acad Sci. These studies emphasized the mediatory effect of type I IFN on glycolysis induction via IFNAR1, Tyk2, and STAT1. This difference is due primarily to the higher ability of female mice to maintain cellular redox homeostasis [28]. New insights into IDO biology in bacterial and viral infections. 2014;10:e1004185. Yuan S, Chu H, Chan JF-W, Ye Z-W, Wen L, Yan B, Lai P-M, Tee K-M, Huang J, Chen D. SREBP-dependent lipidomic reprogramming as a broad-spectrum antiviral target. Biofactors. Google Scholar. Influenza virus drug resistance: a time-sampled population genetics perspective. Symbols used in the Figure: inhibition; unknown mechanism; direct activation; reversible process. 1995;69:148084. Also, IDO induces kynurenine derivation from tryptophan, leading to stimulation of regulatory T cells [141]. Trends Endocrinol Metab. Mainly, interferon (IFN) production following viral infection affects cell function via alteration in amino acid synthesis, membrane composition, and lipid metabolism. PubMedGoogle Scholar. Following infection, glucose uptake and aerobic glycolysis increase in infected cells continually, which results in higher glucose consumption. Clin Infect Dis. Amatore et al. Mechanistically speaking, polyamines appear to play a pivotal role in the processes of RNA transcription and protein translation of viruses, making them a promising target to combat viral infections [133]. Annu Rev Genet. Since the drug resistance in influenza infection is a global concern, research on designing novel therapeutic modalities to tackle pandemics is of particular importance. 2019;1:296305. Subjects: Nephrology, Rheumatology/Musculoskeletal Disorders Topics: It is indicated that higher levels of GSH, antioxidant enzymes such as glutathione peroxidase, and the anti-apoptotic protein Bcl-2 in the lungs of female mice result in superior resistance of these mice to influenza infection. EMBO J. Polymorphonuclear leukocytes in non-insulin-dependent diabetes mellitus: abnormalities in metabolism and function. 2012;2:27686. Cell Death Differ. Indoleamine 2,3 dioxygenase and metabolic control of immune responses. Host defense against viral infection involves interferon mediated down-regulation of sterol biosynthesis. 2017;8:14550. Nature. Also, NO synthase-mediated generation of NO leads to the depletion of L-arginine, thereby reducing the level of polyamines. Many of the metabolic pathways in influenza infections are increasingly changing, dampening of which appears to hamper the virus replication. Recent research on a mouse model showed that influenza infection could affect more than 100 metabolite markers in serum, lung, and bronchoalveolar lavage fluid [8]. Expression of influenza virus hemagglutinin activates transcription factor NF-kappa B. J Virol. CAS Am J Physiol Endocrinol Metab. AKT is able to promote the expression and membrane localization of GLUT1 as well as the function of phosphofructokinase [83, 84]. The pivotal role of pyruvate dehydrogenase kinases in metabolic flexibility. NF-B signaling in inflammation | Signal Transduction and Myc enhances glycolysis by upregulating expression of the glucose transporter GLUT1, glycolytic genes, and lactate dehydrogenase (LDH), as the converter of pyruvate to lactate [77, 78]. J Infect Dis. Hennet T, Peterhans E, Stocker R. Alterations in antioxidant defences in lung and liver of mice infected with influenza a virus. In addition, NO produced by phagocytic cells has antiviral activity that is simultaneous with nonspecific damage of host cells and viral pathogenesis [149]. Munn DH, Mellor AL. Their results revealed the involvement of oxidative and nitrative stress in the pathogenesis of H1N1 influenza virus-induced acute respiratory distress syndrome (ARDS) [15]. Additionally, the NS1 protein can effectively promote the activity of mTORC2, which, in turn, upregulates c-Myc through FoxO inhibition [71]. Influenza is know to produce early and late viral proteins post infections. SREBP1 is shown to be required for the mTORC1-induced increase in the expression of G6PD, which is the rate-limiting enzyme of the PPP oxidative branch [79]. Emergence of multidrug-resistant influenza a(H1N1)pdm09 virus variants in an Immunocompromised child treated with Oseltamivir and Zanamivir. Semenza GL. Regarding the available results, the mechanistic target of rapamycin complex 1 (mTORC1) and mTORC2 signaling can be activated by a variety of influenza virus proteins. government site. Diagnosis and treatment of rhinovirus respiratory infections Allergy/Immunology . Pathway expression methods are also pulling out some respiratory virus signal since LPE produced a non-zero overlap with influenza pathways on 6 out of 8 experiments and time bins and CPE (with . 2004;78:26326. These pathways are important for viral entry, viral replication, viral propagation and apoptosis, and are . In another survey, the delivery of NO to influenza-infected mice could not improve the lung infection and survival of mice, indicating that NO administration was not a suitable treatment strategy for influenza although this was probably due to the difficulty of determining concentrations of NO that are both viricidal and safe in host airways [155]. 2012;36:2431. Under the menu, go to Desktops or Apps, click on Details next to your choice and then select Add to Favorites. Below is a comprehensive list of the clinical pathways at Children's Hospital of Philadelphia (CHOP). DEFINITION OF HYPOTHERMIA Hypothermia is defined as a core body temperature below 35C (95F). Go to: Etiology Early-onset sepsis (EOS) is generally caused by the transmission of pathogens from the female genitourinary system to the newborn or the fetus. Moreover, CEFTC could exert anti-influenza virus effects by regulating the expression of TLR3, IRF3, IFN-, TAK1, and TBK1 in the TLR3 signaling pathway. UNC Children's Diagnosis and Management of Influenza Clinical Pathway. 2015;479:60918. 2013;8:e66546. The outpatient evaluation of febrile infants younger than 90 days of age; the definition of fever in the young infant; the diagnosis, evaluation, and initial management of fever and early-onset sepsis in neonates (younger than seven days of age); and the approach to an ill-appearing infant are discussed separately: Ilyas R, Wallis R, Soilleux EJ, Townsend P, Zehnder D, Tan BK, Sim RB, Lehnert H, Randeva HS, Mitchell DA. Objective: To evaluate targeted killing of hepatocellular carcinoma (HCC) cells by a recombinant oncolytic influenza virus expressing a PD-L1 antibody (rgFlu/PD-L1) and to develop a novel immunotherapy for HCC. 2004;4:76274. 2015;64:84552. Since the influenza virus affects about 20% of the world population annually, preventive and therapeutic approaches require much closer attention. The febrile infant (29 to 90 days of age): Management - UpToDate and followed apoptosis of the cells in 20 h.p.i. PLoS Pathog. Biomed Chromatogr. 2016;143:305060. J Med Virol. However, GSH depletion results in a deviation of the response towards Th2 cells [30]. Regulation of GLUT1 gene transcription by the serine/threonine kinase Akt1. J Cell Sci. Moreover, essential amino acids are demonstrated to decline in infected tissues due to the production of large amounts of viral and cellular proteins. High glucose disrupts oligosaccharide recognition function via competitive inhibition: a potential mechanism for immune dysregulation in diabetes mellitus. Zhang S, Hulver MW, McMillan RP, Cline MA, Gilbert ER. Inactivation leads to a nutritional requirement for organic sulfur. On the other hand, as mentioned earlier, SREBPs are transcription factors that have a critical role in the process of lipogenesis. Free Radic Res. 2017;8:69. Consider influenza shot (killed vaccine) if due, but ideally at least 1 month after cessation of steroids. 2003;17:75860. 1957;100:10918. Mol Cell Biol. 2019;16:79. Results of a study demonstrated that pre-treatment of infected cells with Hochuekkito (a traditional Japanese herbal medicine) could activate both mitochondrial and glycolytic energy metabolism and thereby intensify symptoms [160]. 1977;8:1009. 2013;58:1007. J Gen Virol. PLoS One. CDC Weekly US Map: Influenza Summary Update. proposed a principal correlation between influenza replication and choline lipids metabolism. The clinical pathways are based upon publicly available medical evidence and/or a consensus of medical practitioners at The Childrens Hospital of Philadelphia (CHOP) and are current at the time of publication. J Virol. Description: We constructed a comprehensive map of the influenza A virus ('IAV') life cycle ('FluMap') by undertaking a literature-based, manual curation approach. also showed that an increase in GSH content in organs by affecting GSH-dependent antiviral pathways strengthens the immune system, in particular Th1 cell response, and decreases viral replication [29]. Sanchez EL, Lagunoff M. Viral activation of cellular metabolism. 2008;112:230517. During influenza infection, viral proteins 2016;13:3. Infection of influenza virus can also alter the cellular level and metabolism of purines and pyrimidines [8, 98, 100], and is associated with both increased activities of nucleotide catabolism core enzymes including adenosine deaminase (ADA) and xanthine oxidase (XO) and elevated levels of inosine, hypoxanthine, xanthine, and uric acid in serum and bronchoalveolar lavage fluid. Thus, the ability of IFN to channel the FAs from biosynthesis to catabolism via fatty acid oxidation (FAO) is currently known as a promising antiviral strategy in pDCs [117], which requires further research for more elucidation. Find a Clinical Pathway Filter by Type Emergency ICU Inpatient Outpatient Specialty Care Primary Care New Updated All Clinical Pathways 22q11.2 Hypocalcemia Screening/Treatment, Inpatient and Outpatient Specialty Care Dunning KR, Anastasi MR, Zhang VJ, Russell DL, Robker RL. 2002;169:703944. BEZ235 alters glucose metabolism via blockage of the PI3K/mTOR pathway, and some clinical trials are underway to assess this strategy in cancer therapy (Smith et al., 2012). Recommendations for the evaluation and treatment of fever in children generally use three different age groups: neonates from birth to 28 or 30 days of age, 16, 17 young infants one to three months. 1990;85:73945. Several lines of current evidence have revealed the antiviral activity of type I IFN to be exerted through hampering glucose-derived cholesterol and fatty acid synthesis [121, 122]. Kuiken T, Riteau B, Fouchier R, Rimmelzwaan G. Pathogenesis of influenza virus infections: the good, the bad and the ugly. Dendritic cells, macrophages, and epithelial cells can express IDO [137, 138], and since the primary target for replication of influenza is primarily found to be respiratory epithelial cells, understanding the role of IDO during influenza infection is of particular importance. 2009;35:1420. Biotechnol Bioeng. To E, Broughton BR, Hendricks KS, Vlahos R, Selemidis S. Influenza a virus and TLR7 activation potentiate NOX2 oxidase-dependent ROS production in macrophages. Krycer JR, Sharpe LJ, Luu W, Brown AJ. Unauthorized use of these marks is strictly prohibited. Nat Commun. EBioMedicine. 2011;216:12631. In this review, we first discuss the metabolic abnormalities during influenza infection and then shed light on the role of immunometabolites that regulate cellular metabolism. are considered, If test result is unavailable prior to floor transfer, inpatient team can begin oseltamivir, Know My Rights About Surprise Medical Bills, Recommendations During Oseltamivir Shortage, CDC Prevention and Control with Flu Vaccine, CDC Seasonal Influenza (Flu) Information for Health Professionals, Recommendations for Prevention and Control of Influenza in Children, 2020-2021, Mask, eye protection, HH, gloves for care providers, Pulmonary (e.g., Asthma), cardiac, renal, hepatic, hematologic, metabolic, neurologic, Treatment of low-risk children is not recommended, Oseltamivir is most likely to be effective within 48 hrs of symptom onset, 2022 The Childrens Hospital of Philadelphia. Before Google Scholar. Metabolic changes caused by influenza infection and related mechanisms. Sundqvist A, Bengoechea-Alonso MT, Ye X, Lukiyanchuk V, Jin J, Harper JW, Ericsson J. New Eng J Med. The pentose phosphate shunt, as another glucose . Yeung AW, Terentis AC, King NJ, Thomas SR. Role of indoleamine 2,3-dioxygenase in health and disease. This enzyme inhibition contributes to an erroneous process, which causes significant disruption of glucose oxidation, cellular respiration, and lipid metabolism (Fig. Occup Med (Lond) 2002;52:24147. 2010;84:1151522. 2014;14:5769. 2004;76:88695. 2015;129:60172. Accordingly, these clinical pathways are not intended to constitute medical advice or treatment, or to create a doctor-patient relationship between/among The Childrens Hospital of Philadelphia (CHOP), its physicians and the individual patients in question. Defining the role of hypoxia-inducible factor 1 in cancer biology and therapeutics. Influenza-virus-induced signaling cascades: targets for antiviral therapy? Learner pathways (alpha) We curate and offer all Arcus Education webinar resources into pathways that match the specific uses cases and skill levels of our learner communities. Such polymorphisms in immune system genes may be associated with some metabolic changes and, in turn, may reinforce the metabolic disorders following influenza infection. Genzel Y, Behrendt I, Konig S, Sann H, Reichl U. Metabolism of MDCK cells during cell growth and influenza virus production in large-scale microcarrier culture. Severe infection with H7N9, H7N7, H5N1, or 1918 virus can lead to upregulation of inflammatory cytokine genes along with downregulation of lipid metabolism and coagulation genes [125]. For instance, the sharp increase of proinflammatory cytokines during influenza infection [106] causes decreased hepatic fatty acid -oxidation both in vitro and in vivo [107, 108], most likely through excessive nitric oxide and other related free radicals [109]. Buffinton G, Christen S, Peterhans E, Stocker R. Oxidative stress in lungs of mice infected with influenza a virus. Provided by the Springer Nature SharedIt content-sharing initiative. Reproductive health knowledge, attitudes and practices of Iranian and 2014;19:694701. Although all of these metabolites were shown to be elevated shortly after the infection, 5,6-DHET and 5-oxoETE levels remained considerably high up to 4weeks post-infection, indicating a constant pulmonary inflammation [98]. Frontiers | The C/EBP Homologous Protein (CHOP) Transcription Factor Influenza virus entry New Rochelle: Mary Ann Liebert, Inc.; 2014. In a study by Yamane et al. 2008;89:20809. doi: 10.1128/mBio.02867-19. Burgher Pulgaron Y, Provost C, Pesant MJ, Gagnon CA. Why do cancers have high aerobic glycolysis? Cell. Some metabolic effects of poliomyelitis virus on tissue culture. FASEB BioAdv. -. Immunity. Studies have recently underscored the general effect of IFNs on the energy metabolism of cells, mostly by promoting glycolysis. These results suggested that different doses of influenza virus could cause varying infection symptoms in mice. 1852;2015:2391401. Cell. 2016;44:132536. CDC recommends deferring COVID-19 vaccination for eligible children to 3 months post-MISC and clinical recovery has been achieved, including return to normal cardiac function; and onset of MIS-C occurred before any COVID-19 vaccination. Sci China Life Sci. Trends Immunol. Glutathione (GSH) is a vital antioxidant in the cell, and its cellular content is inversely related to influenza virus replication in the cell [26, 27]. In this respect, extremely low PDH enzyme activity has been found after influenza infection in vitro. 2005;98:0506030001. According to a study, diacyl glycerophosphocholine (PC) and diacyl glycerophosphoethanolamine (PE) species (containing 20:4 or 22:6 as precursors of docosahexaenoic acid (DHA) and arachidonic acid (AA) respectively) are associated with influenza-related diseases. Tisoncik-Go J, Gasper DJ, Kyle JE, Eisfeld AJ, Selinger C, Hatta M, Morrison J, Korth MJ, Zink EM, Kim YM, et al. See this image and copyright information in PMC. Article Takeda N, O'Dea EL, Doedens A, Kim J-W, Weidemann A, Stockmann C, Asagiri M, Simon MC, Hoffmann A, Johnson RS. PLoS One. Nowadays, IDO is hypothesized to be part of the metabolic, immune regulation, which plays a protective role in immune responses and inhibits the overreaction of these responses against influenza infection. Development. Barthel A, Okino ST, Liao J, Nakatani K, Li J, Whitlock JP, Roth RA. 2016;785:449. 2009;15:647983. Also, systemic administration of NOS inhibitor could postpone weight loss and death among 1918 virus-infected mice [154]. J Clin Invest. Evidently, higher production of these complex lipids in the cell will require increased biosynthesis of fatty acids. Increased expression of influenza M2 protein can activate protein kinase C and increase reactive oxygen species (ROS) production [10]. Celestino I, Checconi P, Amatore D, Coluccio P, Dattilo R, Alunni Fegatelli D, Clemente AM, Torcia MG, Matarrese P, Mancinelli R. Differential redox state contributes to sex disparities in the response to influenza virus infection in male and female mice. CAS Cell Host Microbe. Also, activation of macrophages by IFN induces expression of the ATP-citrate lyase enzyme (ACLY), and blockage of ACLY activity reduces the production of ROS and nitric oxide [120]. eCollection 2023 Apr 21. Obesity increases mortality and modulates the lung Metabolome during pandemic H1N1 influenza virus infection in mice. Influenza (Flu) Vaccine Resources | Children's Hospital of Philadelphia Influenza a virus PB1-F2 is involved in regulation of cellular redox state in alveolar epithelial cells. P129; 2011. Stegenga ME, van der Crabben SN, Blmer RM, Levi M, Meijers JC, Serlie MJ, Tanck MW, Sauerwein HP, van der Poll T. Hyperglycemia enhances coagulation and reduces neutrophil degranulation, whereas hyperinsulinemia inhibits fibrinolysis during human endotoxemia. Blanc et al. Continuous nitric oxide synthesis by inducible nitric oxide synthase in normal human airway epithelium in vivo.