Intervirology. The following sections summarize recent evidence about the novel therapeutic approaches that target metabolic pathways in influenza infection. Allergy/Immunology . On the other hand, as mentioned earlier, SREBPs are transcription factors that have a critical role in the process of lipogenesis. IDO expression by dendritic cells: tolerance and tryptophan catabolism. Wise DR, DeBerardinis RJ, Mancuso A, Sayed N, Zhang XY, Pfeiffer HK, Nissim I, Daikhin E, Yudkoff M, McMahon SB, Thompson CB. In a study by Yamane et al. A study has shown that the AM580 compound, which is a retinoid derivative, inhibits SREBP-linked pathways, and it has antiviral activity against influenza A and coronavirus in vitro and in vivo [105]. Front Immunol. Based on information obtained from publicly available pathway databases, updated with literature-based information and input from expert virologists and immunologists, FluMap is . 2012;26:87790. 2014;9:e104605. There exists a coincidence of peak IDO1 and IFN-k expression during influenza infection. Pathways and Resources - Children's Clinical Care Portal There is a strong consensus that influenza replication is crucially dependent on fatty acids [97], which makes it a fascinating target for therapeutic modalities [45]. Children's Surgery Program Guideline for Attending Physician Bedside Presence. IDO is an intracellular enzyme that induces production of kynurenine from L-tryptophan, thereby acting to deplete tryptophan and modulate the immune system following viral infections [134]. dc.contributor.author: Sherafat Kazemzadeh, R. dc.contributor.author: Rezaeie, M. dc.contributor.author Influenza virus infection (IVI) is one of the most common infectious agents, capable of infecting a variety of avian and mammalian species. Moreover, essential amino acids, especially tryptophan, are other materials whose quantities have been shown to decline in infected tissues [112]. Moreover, AKT-dependent inactivation of FoxOs can increase glycolysis [72, 73] by removing the suppressive force of c-Myc [74,75,76]. EMBO J. 2006 Mar-Apr;119(3-4):101-11. Some metabolic effects of poliomyelitis virus on tissue culture. Many of the metabolic pathways in influenza infections are increasingly changing, dampening of which appears to hamper the virus replication. 2011;216:12631. Biochem Biophys Res Commun. Alireza Chaboki - Contact Person Committee - IPhSA Iran | LinkedIn 2013;444:3019. Host defense against viral infection involves interferon mediated down-regulation of sterol biosynthesis. Polymorphonuclear leukocytes in non-insulin-dependent diabetes mellitus: abnormalities in metabolism and function. Such polymorphisms in immune system genes may be associated with some metabolic changes and, in turn, may reinforce the metabolic disorders following influenza infection. Cell. 1998;72:68847. 1958;5:20619. This virus has the ability to induce higher consumption rates of glutamine during glutaminolysis, which can be attributed to transient c-Myc overexpression [9]. Effect of poliomyelitis virus on glycolysis and uptake of glycine by monkey kidney tissue cultures. -, Shaib HA, Cochet N, Ribeiro T, et al. In contrast, IL-1 (rs16944) (GG) and IL-28 (rs8099917) GG and TG genotypes were associated with reduced risk of infection [132]. Flu Infection Reveals Many Paths to Immune Response mTORC1 can up-regulate protein synthesis through several downstream factors [113]. Wang F, Zhang S, Jeon R, Vuckovic I, Jiang X, Lerman A, Folmes CD, Dzeja PD, Herrmann J. Interferon gamma induces reversible metabolic reprogramming of M1 macrophages to sustain cell viability and pro-inflammatory activity. Friel H, Lederman H. A nutritional supplement formula for influenza a (H5N1) infection in humans. 2007;12:10813. FASEB BioAdv. Nitric oxide (NO) is a gaseous free radical with accessible vasodilatory and microbicidal functions [144]. J Virol. Genes Dev. Numata M, Kandasamy P, Nagashima Y, Posey J, Hartshorn K, Woodland D, Voelker DR. Phosphatidylglycerol suppresses influenza a virus infection. The Division of Allergy and Immunology at Children's Hospital of Philadelphia (CHOP) is the largest of its kind in the USA. Sci Rep. 2016;6:26076. Thai M, Graham NA, Braas D, Nehil M, Komisopoulou E, Kurdistani SK, McCormick F, Graeber TG, Christofk HR. These pathogens can ascend the vagina, the cervix, and the uterus, and can also infect the amniotic fluid. 2015;194:484659. Influenza virus inhibits the synthesis of these cellular proteins and facilitates expression of its own proteins for viral transcription and replication. 2010;29:625. 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. 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Since tryptophan is critical for T cell proliferation, depletion of this amino acid by IDO suppresses the immune system through the stimulation of T regulatory cells. Am J Public Health. This multivalent attachment by multiple copies of trimetric HA triggers endocytosis of influenza virus that is contained in the endosome. Uetani et al. van Wissen M, Snoek M, Smids B, Jansen HM, Lutter R. IFN-gamma amplifies IL-6 and IL-8 responses by airway epithelial-like cells via indoleamine 2,3-dioxygenase. 1994;68:31129. J Infect Dis. https://doi.org/10.1186/s11658-020-00211-2, DOI: https://doi.org/10.1186/s11658-020-00211-2. Moreover, CEFTC could exert anti-influenza virus effects by regulating the expression of TLR3, IRF3, IFN-, TAK1, and TBK1 in the TLR3 signaling pathway. International Scientific Literature, Ltd. Am J Chin Med. Uehara EU, Shida Bde S, de Brito CA. Sarawar SR, Doherty PC. Porstmann T, Santos CR, Griffiths B, Cully M, Wu M, Leevers S, Griffiths JR, Chung Y-L, Schulze A. SREBP activity is regulated by mTORC1 and contributes to Akt-dependent cell growth. 1977;8:1009. Boergeling Y, Ludwig S. Targeting a metabolic pathway to fight the flu. Biochim Biophys Acta. This influenza-mediated elevation of AA, consistent with inflammation, has also been reported in the same study [97]. Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. Berl Munch Tierarztl Wochenschr. Biochim Biophys Acta. 2003 Feb;9(2):46-52. doi: 10.1016/s1471-4914(02)00010-2. J Immunol. Nat Commun. Short KR, Kroeze EJV, Fouchier RA, Kuiken T. Pathogenesis of influenza-induced acute respiratory distress syndrome. 2018;46(8):1663-1700. doi: 10.1142/S0192415X18500854. Introduction to the Principles and Practice of Clinical Research 2020-2021 . Systems-level metabolic flux profiling identifies fatty acid synthesis as a target for antiviral therapy. Morgan OW, Bramley A, Fowlkes A, Freedman DS, Taylor TH, Gargiullo P, Belay B, Jain S, Cox C, Kamimoto L. Morbid obesity as a risk factor for hospitalization and death due to 2009 pandemic influenza A (H1N1) disease. Green M, Henle G, Deinhardt F. Respiration and glycolysis of human cells grown in tissue culture. Inflammatory Monocytes Drive Influenza A VirusMediated Lung Injury in Juvenile Mice. An increase in ROS production, along with impaired antioxidant function, ultimately leads to a profound change in redox homeostasis of the cell [16,17,18,19]. The metabolism and concentration of glucose in the cell play a cardinal role in the homeostasis of cellular metabolic procedures [46]. LXI. Vlahos R, Stambas J, Bozinovski S, Broughton BR, Drummond GR, Selemidis S. Inhibition of Nox2 oxidase activity ameliorates influenza a virus-induced lung inflammation. Role of IFN in IDO activation. and transmitted securely. Careers. Amatore D, Sgarbanti R, Aquilano K, Baldelli S, Limongi D, Civitelli L, Nencioni L, Garaci E, Ciriolo MR, Palamara AT. Host cellular signaling induced by influenza virus. It has been demonstrated that catalytic activity of glutaminase, as the key enzyme in glutaminolysis, greatly increases following the infection [63]. The stage of hypothermia, defined by core temperature, has a major impact on both recognition and treatment. 1956;104:27187. Hui KP, Kuok DI, Kang SS, Li HS, Ng MM, Bui CH, Peiris JS, Chan RW, Chan MC. The viral replication has the highest use of ATP during influenza infection, releasing large quantities of energy in the form of heat. Am J Respir Cell Mol Biol. Metabolic host response and therapeutic approaches to influenza 2006;94:66779. Marion-Letellier R, Savoye G, Ghosh S. Fatty acids, eicosanoids and PPAR gamma. Kuss-Duerkop SK, Wang J, Mena I. Beta interferon regulation of glucose metabolism is PI3K/Akt dependent and important for antiviral activity against Coxsackievirus B3. Furthermore, oxidative stress following infection can induce the transcription factor NF-kB, which subsequently leads to increased levels of inflammatory cytokines, including interleukin (IL)-1, IL-6, IFN, and TNF [31, 32]. This process can increase the temperature of infected cells by 45C. PLoS Biol. FDA-approved Abl/EGFR/PDGFR kinase inhibitors show potent efficacy against pandemic and seasonal influenza A virus infections of human lung explants. In: BMC proceedings BioMed Central, vol. Division of Allergy and Immunology | Children's Hospital of Philadelphia J Virol. Ritter JB, Wahl AS, Freund S, Genzel Y, Reichl U. Metabolic effects of influenza virus infection in cultured animal cells: intra-and extracellular metabolite profiling. Med Int. Science. Fatty acids and eicosanoids regulate gene expression through direct interactions with peroxisome proliferator-activated receptors and . Proc Natl Acad Sci. Since the influenza virus affects about 20% of the world population annually, preventive and therapeutic approaches require much closer attention. On the other hand, PB1-F2 decreases superoxide anion dismutase 1 (SOD1) expression and consequently disrupts the ROS scavenging process [11]. New Eng J Med. Interestingly HIF-1-knockout macrophages show decreased expression of iNOS after IFN stimulation [153], indicating the possible involvement of HIF-1 in influenza pathogenesis. Influenza virus replication raises the temperature of cells. Acta Neurol Scand. Hives Clipboard, Search History, and several other advanced features are temporarily unavailable. 2009;122:358994. and followed apoptosis of the cells in 20 h.p.i. Lim J, Oh E, Kim Y, Jung W, Kim H, Lee J, Sul D. Enhanced oxidative damage to DNA, lipids, and proteins and levels of some antioxidant enzymes, cytokines, and heat shock proteins in patients infected with influenza H1N1 virus. A significant decrease in mitochondrial fatty acid -oxidation simultaneously with increased biosynthesis of fatty acids and membrane lipids may reflect the fact that the virus stores structural lipids to produce more infectious particles. In addition, increased temperature of cells during infection (which could be the result of virus replication and fever) causes heat stress which in turn can considerably downregulate carnitine palmitoyltransferase II (CPT II) activity and reduce the -oxidation and ATP levels in fibroblasts of influenza-associated encephalopathy patients and healthy volunteers [110].