Current Clinical Microbiology Reports

, Volume 6, Issue 1, pp 34–43 | Cite as

Pathways to Understanding Virus-Host Metabolism Interactions

  • John G. PurdyEmail author
Virology (A Nicola, Section Editor)
Part of the following topical collections:
  1. Topical Collection on Virology


Purpose of Review

Viruses have vast diversity in terms of virion structure, genomic content, and host. All viruses, however, rely on host metabolism as none encode a metabolic network. Although virus-host metabolism interactions are critical to infection, little is understood regarding viral remodeling of its host metabolic network. Likewise, for most viruses, we have yet to identify if and how viruses govern the activity of metabolic pathways. Fortunately, metabolic analyses are becoming more accessible to virologist, thanks in large part to advances in mass spectrometry-based approaches. A brief overview of virus-metabolism interactions and the current state-of-the-art approaches to metabolomics, lipidomics and metabolic analyses are discussed.

Recent Findings

In the last several years, multiple metabolomic and lipidomic studies during virus infection have been reported. Products of the metabolic network support or limit infection. When considering how viruses interact with host metabolism it is critical for virologist to think beyond their copy of a Biochemistry textbook, as computational and analytical advances in recent years have led to novel discoveries in metabolism. Some of those advances and discoveries are introduced here, with a focus on the recent findings in virus-host metabolism interactions.


Metabolism is important to viral infections beyond simply keeping a cell alive while the virus replicates. Recent advances in tools and methods to dissect metabolism during infection have led to novel findings in infection-induced changes in metabolism. Continued research is necessary to build comprehensive understanding of how viruses interact with their host’s metabolic network.


Viral remodeling Metabolism Metabolomics Lipidomics Mass spectrometry 


Compliance With Ethical Standards

Conflict of Interest

The author declares that he has no conflicts of interest.

Human and Animal Rights and Informed Consent

This article does not contain any studies with human or animal subjects performed by any of the authors.


Papers of particular interest, published recently, have been highlighted as: • Of importance •• Of major importance

  1. 1.
    Munger J, Bennett BD, Parikh A, Feng XJ, McArdle J, Rabitz HA, et al. Systems-level metabolic flux profiling identifies fatty acid synthesis as a target for antiviral therapy. Nat Biotechnol. 2008;26(10):1179–86. Scholar
  2. 2.
    Vastag L, Koyuncu E, Grady SL, Shenk TE, Rabinowitz JD. Divergent effects of human cytomegalovirus and herpes simplex virus-1 on cellular metabolism. PLoS Pathog. 2011;7(7):e1002124. Scholar
  3. 3.
    Rabinowitz JD, Purdy JG, Vastag L, Shenk T, Koyuncu E. Metabolomics in drug target discovery. Cold Spring Harb Symp Quant Biol. 2011;76:235–46. Scholar
  4. 4.
    Delgado T, Sanchez EL, Camarda R, Lagunoff M. Global metabolic profiling of infection by an oncogenic virus: KSHV induces and requires lipogenesis for survival of latent infection. PLoS Pathog. 2012;8(8):e1002866. Scholar
  5. 5.
    Fontaine KA, Camarda R, Lagunoff M. Vaccinia virus requires glutamine but not glucose for efficient replication. J Virol. 2014;88(8):4366–74. Scholar
  6. 6.
    Fontaine KA, Sanchez EL, Camarda R, Lagunoff M. Dengue virus induces and requires glycolysis for optimal replication. J Virol. 2015;89(4):2358–66. Scholar
  7. 7.
    Birungi G, Chen SM, Loy BP, Ng ML, Li SF. Metabolomics approach for investigation of effects of dengue virus infection using the EA.hy926 cell line. J Proteome Res. 2010;9(12):6523–34. Scholar
  8. 8.
    Wu J, Sun L, Chen X, Du F, Shi H, Chen C, et al. Cyclic GMP-AMP is an endogenous second messenger in innate immune signaling by cytosolic DNA. Science. 2013;339(6121):826–30. Scholar
  9. 9.
    •• Sychev ZE, Hu A, DiMaio TA, Gitter A, Camp ND, Noble WS, et al. Integrated systems biology analysis of KSHV latent infection reveals viral induction and reliance on peroxisome mediated lipid metabolism. PLoS Pathog. 2017;13(3):e1006256. This study demonstrates the benefit of using multiple omic approaches. Proteomic and RNAseq data suggested that peroxisomal lipid metabolism may be important for latent infection. The authors demonstrated that peroxisome metabolic enzymes were required for survival of latently infected cells. CrossRefPubMedPubMedCentralGoogle Scholar
  10. 10.
    • Park JO, Rubin SA, Xu YF, Amador-Noguez D, Fan J, Shlomi T, et al. Metabolite concentrations, fluxes and free energies imply efficient enzyme usage. Nat Chem Biol. 2016;12(7):482–9. This study demonstrates the conservation of metabolism by examining E. coli , yeast, and mouse cells. Further, it highlights how standard Biochemistry textbooks oversimplify metabolism. CrossRefPubMedPubMedCentralGoogle Scholar
  11. 11.
    Shenk T, Alwine JC. Human cytomegalovirus: coordinating cellular stress, signaling, and metabolic pathways. Ann Rev Virol. 2014;1(1):355–74. Scholar
  12. 12.
    Goodwin CM, Xu S, Munger J. Stealing the keys to the kitchen: viral manipulation of the host cell metabolic network. Trends Microbiol. 2015;23(12):789–98. Scholar
  13. 13.
    Sanchez EL, Lagunoff M. Viral activation of cellular metabolism. Virology. 2015;479-480:609–18. Scholar
  14. 14.
    Lagunoff M. Activation of cellular metabolism during latent Kaposi’s sarcoma herpesvirus infection. Curr Opin Virol. 2016;19:45–9. Scholar
  15. 15.
    Jordan TX, Randall G. Flavivirus modulation of cellular metabolism. Curr Opin Virol. 2016;19:7–10. Scholar
  16. 16.
    Mushtaq M, Darekar S, Kashuba E. DNA tumor viruses and cell metabolism. Oxidative Med Cell Longev. 2016;2016:6468342. Scholar
  17. 17.
    Eagle H, Habel K. The nutritional requirements for the propagation of poliomyelitis virus by the HeLa cell. J Exp Med. 1956;104(2):271–87.CrossRefGoogle Scholar
  18. 18.
    Baron S, Levy HB. Some metabolic effects of poliomyelitis virus on tissue culture. Nature. 1956;178(4544):1230–1.CrossRefGoogle Scholar
  19. 19.
    Figard PH, Levine AS. Incorporation of labeled precursors into lipids of tumors induced by Rous sarcoma virus. Biochim Biophys Acta. 1966;125(3):428–34.CrossRefGoogle Scholar
  20. 20.
    Venuta S, Rubin H. Sugar transport in normal and Rous sarcoma virus-transformed chick-embryo fibroblasts. Proc Natl Acad Sci U S A. 1973;70(3):653–7.CrossRefGoogle Scholar
  21. 21.
    Steck TL, Kaufman S, Bader JP. Glycolysis in chick embryo cell cultures transformed by Rous sarcoma virus. Cancer Res. 1968;28(8):1611–9.PubMedGoogle Scholar
  22. 22.
    Hollenbaugh JA, Montero C, Schinazi RF, Munger J, Kim B. Metabolic profiling during HIV-1 and HIV-2 infection of primary human monocyte-derived macrophages. Virology. 2016;491:106–14. Scholar
  23. 23.
    Lewis VJ Jr, Scott LV. Nutritional requirements for the production of herpes simplex virus. I. Influence of glucose and glutamine of herpes simplex virus production by HeLa cells. J Bacteriol. 1962;83:475–82.PubMedPubMedCentralGoogle Scholar
  24. 24.
    Courtney RJ, Steiner SM, Benyesh-Melnick M. Effects of 2-deoxy-D-glucose on herpes simplex virus replication. Virology. 1973;52(2):447–55.CrossRefGoogle Scholar
  25. 25.
    Kilbourne ED. Inhibition of influenza virus multiplication with a glucose antimetabolite (2-deoxy-D-glucose). Nature. 1959;183(4656):271–2.CrossRefGoogle Scholar
  26. 26.
    Kaluza G, Schmidt MF, Scholtissek C. Effect of 2-deoxy-D-glucose on the multiplication of Semliki Forest virus and the reversal of the block by mannose. Virology. 1973;54(1):179–89.CrossRefGoogle Scholar
  27. 27.
    Stohrer R, Hunter E. Inhibition of Rous sarcoma virus replication by 2-deoxyglucose and tunicamycin: identification of an unglycosylated env gene product. J Virol. 1979;32(2):412–9.PubMedPubMedCentralGoogle Scholar
  28. 28.
    Grady SL, Purdy JG, Rabinowitz JD, Shenk T. Argininosuccinate synthetase 1 depletion produces a metabolic state conducive to herpes simplex virus 1 infection. Proc Natl Acad Sci U S A. 2013;110(51):E5006–15. Scholar
  29. 29.
    Munger J, Bajad SU, Coller HA, Shenk T, Rabinowitz JD. Dynamics of the cellular metabolome during human cytomegalovirus infection. PLoS Pathog. 2006;2(12):e132. Scholar
  30. 30.
    Chambers JW, Maguire TG, Alwine JC. Glutamine metabolism is essential for human cytomegalovirus infection. J Virol. 2010;84(4):1867–73. Scholar
  31. 31.
    Delgado T, Carroll PA, Punjabi AS, Margineantu D, Hockenbery DM, Lagunoff M. Induction of the Warburg effect by Kaposi’s sarcoma herpesvirus is required for the maintenance of latently infected endothelial cells. Proc Natl Acad Sci U S A. 2010;107(23):10696–701. Scholar
  32. 32.
    Sanchez EL, Carroll PA, Thalhofer AB, Lagunoff M. Latent KSHV infected endothelial cells are glutamine addicted and require glutaminolysis for survival. PLoS Pathog. 2015;11(7):e1005052. Scholar
  33. 33.
    Sanchez EL, Pulliam TH, Dimaio TA, Thalhofer AB, Delgado T, Lagunoff M. Glycolysis, glutaminolysis, and fatty acid synthesis are required for distinct stages of Kaposi’s sarcoma-associated herpesvirus lytic replication. J Virol. 2017;91(10):e02237. Scholar
  34. 34.
    •• McFadden K, Hafez AY, Kishton R, Messinger JE, Nikitin PA, Rathmell JC, et al. Metabolic stress is a barrier to Epstein-Barr virus-mediated B-cell immortalization. Proc Natl Acad Sci U S A. 2016;113(6):E782–90. This study examined metabolic activity using a Seahorse instrument to measure oxygen consumption rate as a readout for oxidative phosphorylation and extracellular acidification rate as a proxy for glycolysis. The authors found that EBV-infected cells undergo growth arrest in part due to decreased oxidative phosphorylation. This work demonstrates the power of metabolism to dictate the overall phenotype of infected cells. CrossRefPubMedPubMedCentralGoogle Scholar
  35. 35.
    Hafez AY, Messinger JE, McFadden K, Fenyofalvi G, Shepard CN, Lenzi GM, et al. Limited nucleotide pools restrict Epstein-Barr virus-mediated B-cell immortalization. Oncogene. 2017;6(6):e349. Scholar
  36. 36.
    Landini MP. Early enhanced glucose uptake in human cytomegalovirus-infected cells. J Gen Virol. 1984;65(Pt 7):1229–32. CrossRefPubMedGoogle Scholar
  37. 37.
    Yu Y, Maguire TG, Alwine JC. Human cytomegalovirus activates glucose transporter 4 expression to increase glucose uptake during infection. J Virol. 2011;85(4):1573–80. Scholar
  38. 38.
    Zhang J, Jia L, Lin W, Yip YL, Lo KW, Lau VM, et al. Epstein-Barr virus-encoded latent membrane protein 1 upregulates glucose transporter 1 transcription via the mTORC1/NF-kappaB signaling pathways. J Virol. 2017;91(6):e02168. Scholar
  39. 39.
    Perera R, Riley C, Isaac G, Hopf-Jannasch AS, Moore RJ, Weitz KW, et al. Dengue virus infection perturbs lipid homeostasis in infected mosquito cells. PLoS Pathog. 2012;8(3):e1002584. Scholar
  40. 40.
    Martin-Acebes MA, Merino-Ramos T, Blazquez AB, Casas J, Escribano-Romero E, Sobrino F, et al. The composition of West Nile virus lipid envelope unveils a role of sphingolipid metabolism in flavivirus biogenesis. J Virol. 2014;88(20):12041–54. Scholar
  41. 41.
    Aktepe TE, Pham H, Mackenzie JM. Differential utilisation of ceramide during replication of the flaviviruses West Nile and dengue virus. Virology. 2015;484:241–50. Scholar
  42. 42.
    Heaton NS, Perera R, Berger KL, Khadka S, Lacount DJ, Kuhn RJ, et al. Dengue virus nonstructural protein 3 redistributes fatty acid synthase to sites of viral replication and increases cellular fatty acid synthesis. Proc Natl Acad Sci U S A. 2010;107(40):17345–50. Scholar
  43. 43.
    Heaton NS, Randall G. Dengue virus-induced autophagy regulates lipid metabolism. Cell Host Microbe. 2010;8(5):422–32. Scholar
  44. 44.
    • Jordan TX, Randall G. Dengue virus activates the AMP kinase-mTOR axis to stimulate a proviral lipophagy. J Virol. 2017;91(11):e02020. This work demonstrates that dengue virus replication activates AMPK to increase catabolism of droplet stored lipids. The authors also found that infection disrupts the normal relation between AMPK and mTOR signaling. CrossRefPubMedPubMedCentralGoogle Scholar
  45. 45.
    Thai M, Graham NA, Braas D, Nehil M, Komisopoulou E, Kurdistani SK, et al. Adenovirus E4ORF1-induced MYC activation promotes host cell anabolic glucose metabolism and virus replication. Cell Metab. 2014;19(4):694–701. Scholar
  46. 46.
    Greseth MD, Traktman P. De novo fatty acid biosynthesis contributes significantly to establishment of a bioenergetically favorable environment for vaccinia virus infection. PLoS Pathog. 2014;10(3):e1004021. Scholar
  47. 47.
    Mazzon M, Castro C, Roberts LD, Griffin JL, Smith GL. A role for vaccinia virus protein C16 in reprogramming cellular energy metabolism. J Gen Virol. 2015;96(Pt 2):395–407. CrossRefPubMedPubMedCentralGoogle Scholar
  48. 48.
    Yuan J, Bennett BD, Rabinowitz JD. Kinetic flux profiling for quantitation of cellular metabolic fluxes. Nat Protoc. 2008;3(8):1328–40. Scholar
  49. 49.
    Zamboni N, Saghatelian A, Patti GJ. Defining the metabolome: size, flux, and regulation. Mol Cell. 2015;58(4):699–706. Scholar
  50. 50.
    Buescher JM, Antoniewicz MR, Boros LG, Burgess SC, Brunengraber H, Clish CB, et al. A roadmap for interpreting (13)C metabolite labeling patterns from cells. Curr Opin Biotechnol. 2015;34:189–201. Scholar
  51. 51.
    Koyuncu E, Purdy JG, Rabinowitz JD, Shenk T. Saturated very long chain fatty acids are required for the production of infectious human cytomegalovirus progeny. PLoS Pathog. 2013;9(5):e1003333. Scholar
  52. 52.
    • Purdy JG, Shenk T, Rabinowitz JD. Fatty acid elongase 7 catalyzes lipidome remodeling essential for human cytomegalovirus replication. Cell Rep. 2015;10(8):1375–85. This study is the first to demonstrate that fatty acid elongase 7 is required for viral infection. The work uses a combination of fatty acid abundance measurements using LC-MS along with isotopic tracers and genetic knockdown to determine metabolic activity. CrossRefPubMedPubMedCentralGoogle Scholar
  53. 53.
    Spencer CM, Schafer XL, Moorman NJ, Munger J. Human cytomegalovirus induces the activity and expression of acetyl-coenzyme A carboxylase, a fatty acid biosynthetic enzyme whose inhibition attenuates viral replication. J Virol. 2011;85(12):5814–24. Scholar
  54. 54.
    Yu Y, Maguire TG, Alwine JC. Human cytomegalovirus infection induces adipocyte-like lipogenesis through activation of sterol regulatory element binding protein 1. J Virol. 2012;86(6):2942–9. Scholar
  55. 55.
    Petersen J, Drake MJ, Bruce EA, Riblett AM, Didigu CA, Wilen CB, et al. The major cellular sterol regulatory pathway is required for Andes virus infection. PLoS Pathog. 2014;10(2):e1003911. Scholar
  56. 56.
    Rolland M, Li X, Sellier Y, Martin H, Perez-Berezo T, Rauwel B, et al. PPARgamma is activated during congenital cytomegalovirus infection and inhibits neuronogenesis from human neural stem cells. PLoS Pathog. 2016;12(4):e1005547. Scholar
  57. 57.
    Altindis E, Cai W, Sakaguchi M, Zhang F, GuoXiao W, Liu F, et al. Viral insulin-like peptides activate human insulin and IGF-1 receptor signaling: a paradigm shift for host-microbe interactions. Proc Natl Acad Sci U S A. 2018;115(10):2461–6. Scholar
  58. 58.
    Haeusler RA, McGraw TE, Accili D. Biochemical and cellular properties of insulin receptor signalling. Nat Rev Mol Cell Biol. 2018;19(1):31–44. Scholar
  59. 59.
    Chuang C, Prasanth KR, Nagy PD. The glycolytic pyruvate kinase is recruited directly into the viral replicase complex to generate ATP for RNA synthesis. Cell Host Microbe. 2017;22(5):639–52.e7. Scholar
  60. 60.
    Munday MR. Regulation of mammalian acetyl-CoA carboxylase. Biochem Soc Trans. 2002;30(Pt 6):1059–64.CrossRefGoogle Scholar
  61. 61.
    Meredith MJ, Lane MD. Acetyl-CoA carboxylase. Evidence for polymeric filament to protomer transition in the intact avian liver cell. J Biol Chem. 1978;253(10):3381–3.PubMedGoogle Scholar
  62. 62.
    Soto-Acosta R, Bautista-Carbajal P, Cervantes-Salazar M, Angel-Ambrocio AH, Del Angel RM. DENV up-regulates the HMG-CoA reductase activity through the impairment of AMPK phosphorylation: a potential antiviral target. PLoS Pathog. 2017;13(4):e1006257. Scholar
  63. 63.
    Merino-Ramos T, Vazquez-Calvo A, Casas J, Sobrino F, Saiz JC, Martin-Acebes MA. Modification of the host cell lipid metabolism induced by hypolipidemic drugs targeting the acetyl coenzyme a carboxylase impairs West Nile virus replication. Antimicrob Agents Chemother. 2016;60(1):307–15. Scholar
  64. 64.
    McArdle J, Moorman NJ, Munger J. HCMV targets the metabolic stress response through activation of AMPK whose activity is important for viral replication. PLoS Pathog. 2012;8(1):e1002502. Scholar
  65. 65.
    Terry LJ, Vastag L, Rabinowitz JD, Shenk T. Human kinome profiling identifies a requirement for AMP-activated protein kinase during human cytomegalovirus infection. Proc Natl Acad Sci U S A. 2012;109(8):3071–6. Scholar
  66. 66.
    Moser TS, Schieffer D, Cherry S. AMP-activated kinase restricts Rift Valley fever virus infection by inhibiting fatty acid synthesis. PLoS Pathog. 2012;8(4):e1002661. Scholar
  67. 67.
    •• Hackett SR, Zanotelli VR, Xu W, Goya J, Park JO, Perlman DH, et al. Systems-level analysis of mechanisms regulating yeast metabolic flux. Science. 2016;354(6311):aaf2786. This study integrated advanced metabolomics and proteomics techniques along with computational modeling of metabolic activity to determine metabolic regulating steps. Using this approach, new points of metabolic regulation were identified. CrossRefPubMedPubMedCentralGoogle Scholar
  68. 68.
    Bennett BD, Kimball EH, Gao M, Osterhout R, Van Dien SJ, Rabinowitz JD. Absolute metabolite concentrations and implied enzyme active site occupancy in Escherichia coli. Nat Chem Biol. 2009;5(8):593–9. Scholar
  69. 69.
    Reaves ML, Young BD, Hosios AM, Xu YF, Rabinowitz JD. Pyrimidine homeostasis is accomplished by directed overflow metabolism. Nature. 2013;500(7461):237–41. Scholar
  70. 70.
    Lu W, Kimball E, Rabinowitz JD. A high-performance liquid chromatography-tandem mass spectrometry method for quantitation of nitrogen-containing intracellular metabolites. J Am Soc Mass Spectrom. 2006;17(1):37–50. Scholar
  71. 71.
    •• Lu W, Su X, Klein MS, Lewis IA, Fiehn O, Rabinowitz JD. Metabolite measurement: Pitfalls to avoid and practices to follow. Annu Rev Biochem. 2017;86:277–304. This well-written review provides multiple challenges and considerations that should be addressed in developing metabolomic methods in order to generate interpretable data in a rigorous fashion. The authors also provide many helpful tips to those new to metabolomics. CrossRefPubMedPubMedCentralGoogle Scholar
  72. 72.
    Xu YF, Lu W, Rabinowitz JD. Avoiding misannotation of in-source fragmentation products as cellular metabolites in liquid chromatography-mass spectrometry-based metabolomics. Anal Chem. 2015;87(4):2273–81. Scholar
  73. 73.
    Dang L, White DW, Gross S, Bennett BD, Bittinger MA, Driggers EM, et al. Cancer-associated IDH1 mutations produce 2-hydroxyglutarate. Nature. 2009;462(7274):739–44. Scholar
  74. 74.
    Lu W, Clasquin MF, Melamud E, Amador-Noguez D, Caudy AA, Rabinowitz JD. Metabolomic analysis via reversed-phase ion-pairing liquid chromatography coupled to a stand alone orbitrap mass spectrometer. Anal Chem. 2010;82(8):3212–21. Scholar
  75. 75.
    Slatter DA, Aldrovandi M, O’Connor A, Allen SM, Brasher CJ, Murphy RC, et al. Mapping the human platelet lipidome reveals cytosolic phospholipase A2 as a regulator of mitochondrial bioenergetics during activation. Cell Metab. 2016;23(5):930–44. Scholar
  76. 76.
    Williams PE, Klein DR, Greer SM, Brodbelt JS. Pinpointing double bond and sn-positions in glycerophospholipids via hybrid 193 nm ultraviolet photodissociation (UVPD) mass spectrometry. J Am Chem Soc. 2017;139(44):15681–90. Scholar
  77. 77.
    Adams KJ, Smith NF, Ramirez CE, Fernandez-Lima F. Discovery and targeted monitoring of polychlorinated biphenyl metabolites in blood plasma using LC-TIMS-TOF MS. Int J Mass Spectrom. 2018;427:133–40. Scholar
  78. 78.
    Poad BLJ, Zheng X, Mitchell TW, Smith RD, Baker ES, Blanksby SJ. Online ozonolysis combined with ion mobility-mass spectrometry provides a new platform for lipid isomer analyses. Anal Chem. 2018;90(2):1292–300. Scholar
  79. 79.
    Zheng X, Smith RD, Baker ES. Recent advances in lipid separations and structural elucidation using mass spectrometry combined with ion mobility spectrometry, ion-molecule reactions and fragmentation approaches. Curr Opin Chem Biol. 2018;42:111–8. Scholar
  80. 80.
    Breitkopf SB, Yuan M, Helenius KP, Lyssiotis CA, Asara JM. Triomics analysis of imatinib-treated myeloma cells connects kinase inhibition to RNA processing and decreased lipid biosynthesis. Anal Chem. 2015;87(21):10995–1006. Scholar
  81. 81.
    Hwang J, Purdy JG, Wu K, Rabinowitz JD, Shenk T. Estrogen-related receptor alpha is required for efficient human cytomegalovirus replication. Proc Natl Acad Sci U S A. 2014;111(52):E5706–15. Scholar
  82. 82.
    McArdle J, Schafer XL, Munger J. Inhibition of calmodulin-dependent kinase kinase blocks human cytomegalovirus-induced glycolytic activation and severely attenuates production of viral progeny. J Virol. 2011;85(2):705–14. Scholar
  83. 83.
    Schoeman JC, Hou J, Harms AC, Vreeken RJ, Berger R, Hankemeier T, et al. Metabolic characterization of the natural progression of chronic hepatitis B. Genome Med. 2016;8(1):64. CrossRefPubMedPubMedCentralGoogle Scholar
  84. 84.
    Cui L, Lee YH, Kumar Y, Xu F, Lu K, Ooi EE, et al. Serum metabolome and lipidome changes in adult patients with primary dengue infection. PLoS Negl Trop Dis. 2013;7(8):e2373. Scholar
  85. 85.
    Cui L, Hou J, Fang J, Lee YH, Costa VV, Wong LH, et al. Serum metabolomics investigation of humanized mouse model of dengue virus infection. J Virol. 2017;91(14):e00386. Scholar
  86. 86.
    Buck MD, Sowell RT, Kaech SM, Pearce EL. Metabolic instruction of immunity. Cell. 2017;169(4):570–86. Scholar
  87. 87.
    McKinney EF, Smith KGC. Metabolic exhaustion in infection, cancer and autoimmunity. Nat Immunol. 2018;19(3):213–21. Scholar
  88. 88.
    Ramiere C, Rodriguez J, Enache LS, Lotteau V, Andre P, Diaz O. Activity of hexokinase is increased by its interaction with hepatitis C virus protein NS5A. J Virol. 2014;88(6):3246–54. Scholar
  89. 89.
    Kim SJ, Khan M, Quan J, Till A, Subramani S, Siddiqui A. Hepatitis B virus disrupts mitochondrial dynamics: induces fission and mitophagy to attenuate apoptosis. PLoS Pathog. 2013;9(12):e1003722. Scholar
  90. 90.
    Kim SJ, Syed GH, Khan M, Chiu WW, Sohail MA, Gish RG, et al. Hepatitis C virus triggers mitochondrial fission and attenuates apoptosis to promote viral persistence. Proc Natl Acad Sci U S A. 2014;111(17):6413–8. Scholar
  91. 91.
    Cavallari I, Scattolin G, Silic-Benussi M, Raimondi V, D’Agostino DM, Ciminale V. Mitochondrial proteins coded by human tumor viruses. Front Microbiol. 2018;9:81. Scholar
  92. 92.
    Mukherjee A, Patra U, Bhowmick R, Chawla-Sarkar M. Rotaviral nonstructural protein 4 triggers dynamin-related protein 1-dependent mitochondrial fragmentation during infection. Cell Microbiol. 2018;20(6):e12831. Scholar
  93. 93.
    Yogev O, Lagos D, Enver T, Boshoff C. Kaposi’s sarcoma herpesvirus microRNAs induce metabolic transformation of infected cells. PLoS Pathog. 2014;10(9):e1004400. Scholar
  94. 94.
    Bhuvanendran S, Salka K, Rainey K, Sreetama SC, Williams E, Leeker M, et al. Superresolution imaging of human cytomegalovirus vMIA localization in sub-mitochondrial compartments. Viruses. 2014;6(4):1612–36. Scholar
  95. 95.
    Reeves MB, Davies AA, McSharry BP, Wilkinson GW, Sinclair JH. Complex I binding by a virally encoded RNA regulates mitochondria-induced cell death. Science. 2007;316(5829):1345–8. Scholar
  96. 96.
    Vazquez C, Horner SM. MAVS coordination of antiviral innate immunity. J Virol. 2015;89(14):6974–7. Scholar
  97. 97.
    Alwine JC. Modulation of host cell stress responses by human cytomegalovirus. Curr Top Microbiol Immunol. 2008;325:263–79.PubMedGoogle Scholar
  98. 98.
    DeBerardinis RJ, Lum JJ, Hatzivassiliou G, Thompson CB. The biology of cancer: metabolic reprogramming fuels cell growth and proliferation. Cell Metab. 2008;7(1):11–20. Scholar
  99. 99.
    Cantor JR, Sabatini DM. Cancer cell metabolism: one hallmark, many faces. Cancer Discov. 2012;2(10):881–98. Scholar
  100. 100.
    Ripoli M, D’Aprile A, Quarato G, Sarasin-Filipowicz M, Gouttenoire J, Scrima R, et al. Hepatitis C virus-linked mitochondrial dysfunction promotes hypoxia-inducible factor 1 alpha-mediated glycolytic adaptation. J Virol. 2010;84(1):647–60. Scholar

Copyright information

© Springer Nature Switzerland AG 2018

Authors and Affiliations

  1. 1.Department of Immunobiology and BIO5 InstituteUniversity of ArizonaTucsonUSA

Personalised recommendations