Glucose and glutamine drive hepatitis E virus replication.
Glutaminolysis
Glycolysis
HSP70
HSP90
Hepatitis E virus
Hexosamine biosynthetic pathway
Journal
Archives of virology
ISSN: 1432-8798
Titre abrégé: Arch Virol
Pays: Austria
ID NLM: 7506870
Informations de publication
Date de publication:
30 Oct 2024
30 Oct 2024
Historique:
received:
08
05
2024
accepted:
03
09
2024
medline:
31
10
2024
pubmed:
30
10
2024
entrez:
30
10
2024
Statut:
epublish
Résumé
Viruses have undergone evolutionary adaptations to tune their utilization of carbon sources, enabling them to extract specific cellular substrates necessary for their replication. The lack of a reliable cell culture system and a small-animal model has hampered our understanding of the molecular mechanism of replication of hepatitis E virus (HEV) genotype 1. Our recent identification of a replicative ensemble of mutant HEV RNA libraries has allowed us to study the metabolic prerequisites for HEV replication. Initial assessments revealed increased glucose and glutamine utilization during HEV replication. Inhibition of glycolysis and glycolysis + glutaminolysis reduced the levels of HEV replication to similar levels. An integrated analysis of protein-metabolite pathways suggests that HEV replication markedly alters glycolysis, the TCA cycle, and glutamine-associated metabolic pathways. Cells supporting HEV replication showed a requirement for fructose-6-phosphate and glutamine utilization through the hexosamine biosynthetic pathway (HBP), stimulating HSP70 expression to facilitate virus replication. Observations of mannose utilization and glutamine dependence suggest a crucial role of the HBP in supporting HEV replication. Inhibition of glycolysis and HSP70 activity or knockdown of glutamine fructose-6-phosphate amidotransferase expression led to a substantial reduction in HEV RNA and ORF2 expression accompanied by a significant decrease in HSP70 levels. This study demonstrates that glucose and glutamine play critical roles in facilitating HEV replication.
Identifiants
pubmed: 39476184
doi: 10.1007/s00705-024-06160-x
pii: 10.1007/s00705-024-06160-x
doi:
Substances chimiques
Glutamine
0RH81L854J
Glucose
IY9XDZ35W2
RNA, Viral
0
HSP70 Heat-Shock Proteins
0
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
233Subventions
Organisme : Indian Council of Medical Research
ID : VIR/1/2019/ECD-1
Informations de copyright
© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Austria, part of Springer Nature.
Références
Sanchez EL, Lagunoff M (2015) Viral activation of cellular metabolism. Virology 479–480:609–618. https://doi.org/10.1016/j.virol.2015.02.038
doi: 10.1016/j.virol.2015.02.038
pubmed: 25812764
Wise DR, DeBerardinis RJ, Mancuso A et al (2008) Myc regulates a transcriptional program that stimulates mitochondrial glutaminolysis and leads to glutamine addiction. Proc Natl Acad Sci 105:18782–18787. https://doi.org/10.1073/pnas.0810199105
doi: 10.1073/pnas.0810199105
pubmed: 19033189
pmcid: 2596212
DeBerardinis RJ, Mancuso A, Daikhin E et al (2007) Beyond aerobic glycolysis: Transformed cells can engage in glutamine metabolism that exceeds the requirement for protein and nucleotide synthesis. Proc Natl Acad Sci 104:19345–19350. https://doi.org/10.1073/pnas.0709747104
doi: 10.1073/pnas.0709747104
pubmed: 18032601
pmcid: 2148292
Chambers JW, Maguire TG, Alwine JC (2010) Glutamine metabolism is essential for human cytomegalovirus infection. J Virol 84:1867–1873. https://doi.org/10.1128/JVI.02123-09
doi: 10.1128/JVI.02123-09
pubmed: 19939921
Fontaine KA, Camarda R, Lagunoff M (2014) Vaccinia virus requires glutamine but not glucose for efficient replication. J Virol 88:4366–4374. https://doi.org/10.1128/JVI.03134-13
doi: 10.1128/JVI.03134-13
pubmed: 24501408
pmcid: 3993723
Fontaine KA, Sanchez EL, Camarda R, Lagunoff M (2015) Dengue virus induces and requires glycolysis for optimal replication. J Virol 89:2358–2366. https://doi.org/10.1128/JVI.02309-14
doi: 10.1128/JVI.02309-14
pubmed: 25505078
Gualdoni GA, Mayer KA, Kapsch A-M et al (2018) Rhinovirus induces an anabolic reprogramming in host cell metabolism essential for viral replication. Proc Natl Acad Sci U S A 115:E7158–E7165. https://doi.org/10.1073/pnas.1800525115
doi: 10.1073/pnas.1800525115
pubmed: 29987044
pmcid: 6065033
Ramière C, Rodriguez J, Enache LS et al (2014) Activity of Hexokinase Is Increased by Its Interaction with Hepatitis C Virus Protein NS5A. J Virol 88:3246–3254. https://doi.org/10.1128/jvi.02862-13
doi: 10.1128/jvi.02862-13
pubmed: 24390321
pmcid: 3957934
Huang R, Huestis M, Gan ES et al (2021) Hypoxia and viral infectious diseases. JCI insight 6:e147190. https://doi.org/10.1172/jci.insight.147190
doi: 10.1172/jci.insight.147190
pubmed: 33830079
pmcid: 8119216
Ji W-T, Liu HJ (2008) PI3K-Akt signaling and viral infection. Recent Pat Biotechnol 2:218–226. https://doi.org/10.2174/187220808786241042
doi: 10.2174/187220808786241042
pubmed: 19097333
Santoro MG, Amici C, Rossi A (2009) Role of Heat Shock Proteins in Viral Infection. Prokaryotic Eukaryot Heat Shock Proteins Infect Dis 4:51–84. https://doi.org/10.1007/978-90-481-2976-8_3
doi: 10.1007/978-90-481-2976-8_3
Moin SM, Chandra V, Arya R, Jameel S (2009) The hepatitis E virus ORF3 protein stabilizes HIF-1α and enhances HIF-1-mediated transcriptional activity through p300/CBP. Cell Microbiol 11:1409–1421. https://doi.org/10.1111/j.1462-5822.2009.01340.x
doi: 10.1111/j.1462-5822.2009.01340.x
pubmed: 19489936
Kanade GD, Pingale KD, Karpe YA (2019) Protein Interactions Network of Hepatitis E Virus RNA and Polymerase With Host Proteins. Front Microbiol 10:2501. https://doi.org/10.3389/fmicb.2019.02501
doi: 10.3389/fmicb.2019.02501
pubmed: 31736926
pmcid: 6838024
Girdhar K, Powis A, Raisingani A et al (2021) Viruses and Metabolism: The Effects of Viral Infections and Viral Insulins on Host Metabolism. Annu Rev Virol 8:373–391. https://doi.org/10.1146/annurev-virology-091919-102416
doi: 10.1146/annurev-virology-091919-102416
pubmed: 34586876
pmcid: 9175272
Hepatitis E (2022) Who int. https://www.who.int/news-room/fact-sheets/detail/hepatitis-e . Accessed 21 June 2023
Goel A, Padmaprakash V, Benjamin K M, et al (2020) Temporal profile of HEV RNA concentration in blood and stool from patients with acute uncomplicated hepatitis E in a region with genotype 1 predominance. J Viral Hepat 27:631–637. https://doi.org/10.1111/jvh.13266
doi: 10.1111/jvh.13266
pubmed: 31997507
Khan S, Kumar Y, Sharma C et al (2023) Dysregulated metabolites and lipids in serum of patients with acute hepatitis E: A longitudinal study. J Viral Hepat 30:959–969. https://doi.org/10.1111/jvh.13885
doi: 10.1111/jvh.13885
pubmed: 37697495
Agarwal S, Baccam P, Aggarwal R, Veerapu NS (2018) Novel Synthesis and Phenotypic Analysis of Mutant Clouds for Hepatitis E Virus Genotype 1. J Virol 92:e01932–e01917. https://doi.org/10.1128/JVI.01932-17
doi: 10.1128/JVI.01932-17
pubmed: 29167341
pmcid: 5790927
Hamiel CR, Pinto S, Hau A, Wischmeyer PE (2009) Glutamine enhances heat shock protein 70 expression via increased hexosamine biosynthetic pathway activity. Am J Physiol Cell Physiol 297:C1509–1519. https://doi.org/10.1152/ajpcell.00240.2009
doi: 10.1152/ajpcell.00240.2009
pubmed: 19776393
pmcid: 2793053
Eisenreich W, Rudel T, Heesemann J, Goebel W (2019) How Viral and Intracellular Bacterial Pathogens Reprogram the Metabolism of Host Cells to Allow Their Intracellular Replication. Front Cell Infect Microbiol 9:42. https://doi.org/10.3389/fcimb.2019.00042
doi: 10.3389/fcimb.2019.00042
pubmed: 30886834
pmcid: 6409310
Jothikumar N, Cromeans TL, Robertson BH et al (2006) A broadly reactive one-step real-time RT-PCR assay for rapid and sensitive detection of hepatitis E virus. J Virol Methods 131:65–71. https://doi.org/10.1016/j.jviromet.2005.07.004
doi: 10.1016/j.jviromet.2005.07.004
pubmed: 16125257
Mayer KA, Stöckl J, Zlabinger GJ, Gualdoni GA (2019) Hijacking the Supplies: Metabolism as a Novel Facet of Virus-Host Interaction. Front Immunol 10:1533. https://doi.org/10.3389/fimmu.2019.01533
doi: 10.3389/fimmu.2019.01533
pubmed: 31333664
pmcid: 6617997
Cardaci S, Desideri E, Ciriolo MR (2012) Targeting aerobic glycolysis: 3-bromopyruvate as a promising anticancer drug. J Bioenerg Biomembr 44:17–29. https://doi.org/10.1007/s10863-012-9422-7
doi: 10.1007/s10863-012-9422-7
pubmed: 22328057
Katt WP, Cerione RA (2014) Glutaminase regulation in cancer cells: a druggable chain of events. Drug Discov Today 19:450–457. https://doi.org/10.1016/j.drudis.2013.10.008
doi: 10.1016/j.drudis.2013.10.008
pubmed: 24140288
Qiao D, Skibba M, Xu X et al (2021) Paramyxovirus replication induces the hexosamine biosynthetic pathway and mesenchymal transition via the IRE1α-XBP1s arm of the unfolded protein response. Am J Physiol - Lung Cell Mol Physiol 321:L576–L594. https://doi.org/10.1152/ajplung.00127.2021
doi: 10.1152/ajplung.00127.2021
pubmed: 34318710
pmcid: 8461800
Zhang X, Yu W (2022) Heat shock proteins and viral infection. Front Immunol 13:947789. https://doi.org/10.3389/fimmu.2022.947789
doi: 10.3389/fimmu.2022.947789
pubmed: 35990630
pmcid: 9389079
Marshall S, Bacote V, Traxinger RR (1991) Discovery of a metabolic pathway mediating glucose-induced desensitization of the glucose transport system. {Role} of hexosamine biosynthesis in the induction of insulin resistance. J Biol Chem 266:4706–4712
doi: 10.1016/S0021-9258(19)67706-9
pubmed: 2002019
Marshall S, Nadeau O, Yamasaki K (2004) Dynamic Actions of Glucose and Glucosamine on Hexosamine Biosynthesis in Isolated Adipocytes. J Biol Chem 279:35313–35319. https://doi.org/10.1074/jbc.M404133200
doi: 10.1074/jbc.M404133200
pubmed: 15199059
Chiaradonna F, Ricciardiello F, Palorini R (2018) The Nutrient-Sensing Hexosamine Biosynthetic Pathway as the Hub of Cancer Metabolic Rewiring. Cells 7:53. https://doi.org/10.3390/cells7060053
doi: 10.3390/cells7060053
pubmed: 29865240
pmcid: 6025041
Sumbria D, Berber E, Mathayan M, Rouse BT (2020) Virus Infections and Host Metabolism-Can We Manage the Interactions? Front Immunol 11:594963. https://doi.org/10.3389/fimmu.2020.594963
doi: 10.3389/fimmu.2020.594963
pubmed: 33613518
Chatham JC, Nöt LG, Fülöp N, Marchase RB (2008) Hexosamine biosynthesis and protein O-glycosylation: the first line of defense against stress, ischemia, and trauma. Shock 29:431–440. https://doi.org/10.1097/shk.0b013e3181598bad
doi: 10.1097/shk.0b013e3181598bad
pubmed: 17909453
Grigorian A, Lee S-U, Tian W et al (2007) Control of T Cell-mediated autoimmunity by metabolite flux to N-glycan biosynthesis. J Biol Chem 282:20027–20035. https://doi.org/10.1074/jbc.M701890200
doi: 10.1074/jbc.M701890200
pubmed: 17488719
Xue H, Slavov D, Wischmeyer PE (2012) Glutamine-mediated Dual Regulation of Heat Shock Transcription Factor-1 Activation and Expression. J Biol Chem 287:40400–40413. https://doi.org/10.1074/jbc.M112.410712
doi: 10.1074/jbc.M112.410712
pubmed: 23055521
pmcid: 3504755
Goldberg HJ, Whiteside CI, Hart GW, Fantus IG (2006) Erratum: Posttranslational, reversible O-glycosylation is stimulated by high glucose and mediates plasminogen activator inhibitor-1 PAI-1 gene expression and Sp1 transcriptional activity in glomerular mesangial cells Endocrinology (2006) 147. Endocrinology 147
Mercier PA, Winegarden NA, Westwood JT (1999) Human heat shock factor 1 is predominantly a nuclear protein before and after heat stress. J Cell Sci 112:2765–2774. https://doi.org/10.1242/jcs.112.16.2765
doi: 10.1242/jcs.112.16.2765
pubmed: 10413683
Lubkowska A, Pluta W, Strońska A, Lalko A (2021) Role of Heat Shock Proteins HSP70and HSP90 in Viral Infection. Int J Mol Sci 22:9366. https://doi.org/10.3390/ijms22179366
doi: 10.3390/ijms22179366
pubmed: 34502274
pmcid: 8430838
Bolhassani A, Agi E (2019) Heat shock proteins in infection. Clin Chim Acta 498:90–100. https://doi.org/10.1016/j.cca.2019.08.015
doi: 10.1016/j.cca.2019.08.015
pubmed: 31437446
Naito T, Momose F, Kawaguchi A, Nagata K (2007) Involvement of Hsp90 in Assembly and Nuclear Import of Influenza Virus RNA Polymerase Subunits. J Virol 81:1339–1349. https://doi.org/10.1128/JVI.01917-06
doi: 10.1128/JVI.01917-06
pubmed: 17121807
Li G, Zhang J, Tong X et al (2011) Heat shock protein 70 inhibits the activity of Influenza A virus ribonucleoprotein and blocks the replication of virus in vitro and in vivo. PLoS ONE 6:e16546. https://doi.org/10.1371/journal.pone.0016546
doi: 10.1371/journal.pone.0016546
pubmed: 21390211
pmcid: 3044721
John L, Thomas S, Herchenröder O et al (2011) Hepatitis E virus ORF2 protein activates the pro-apoptotic gene CHOP and anti-apoptotic heat shock proteins. PLoS ONE 6:e25378. https://doi.org/10.1371/journal.pone.0025378
doi: 10.1371/journal.pone.0025378
pubmed: 21966512
pmcid: 3179511
Zheng Z-Z, Miao J, Zhao M et al (2010) Role of heat-shock protein 90 in hepatitis E virus capsid trafficking. J Gen Virol 91:1728–1736. https://doi.org/10.1099/vir.0.019323-0
doi: 10.1099/vir.0.019323-0
pubmed: 20219895
Shen Q, Pu Y, Fu X et al (2014) Changes in the cellular proteins of {A549} infected with hepatitis E virus by proteomics analysis. BMC Vet Res 10:188. https://doi.org/10.1186/s12917-014-0188-5
doi: 10.1186/s12917-014-0188-5
pubmed: 25175408
pmcid: 4236826