Nuclear receptors control pro-viral and antiviral metabolic responses to hepatitis C virus infection

Nature Chemical Biology

Volumn 12, Issue 12, 2016, Pages 1037-1045

  Levy, Gahl ^a   Habib, Naomi ^a,b   Guzzardi, Maria Angela ^a,c   Kitsberg, Daniel ^a   Bomze, David ^a   Ezra, Elishai ^a,d   Uygun, Basak E ^e   Uygun, Korkut ^e   Trippler, Martin ^f   Schlaak, Joerg F ^f   Shibolet, Oren ^g   Sklan, Ella H ^h   Cohen, Merav ^a   Timm, Joerg ⁱ   Friedman, Nir ^a   Nahmias, Yaakov ^a  

^a HEBREW UNIVERSITY OF JERUSALEM   (Israel)

^b BROAD INSTITUTE OF MIT AND HARVARD   (United States)

^c INSTITUTE OF CLINICAL PHYSIOLOGY   (Italy)

^d JERUSALEM COLLEGE OF TECHNOLOGY   (Israel)

^e MASSACHUSETTS GENERAL HOSPITAL   (United States)

^f UNIVERSITY OF DUISBURG ESSEN   (Germany)

^g TEL AVIV SOURASKY MEDICAL CENTER   (Israel)

^h TEL AVIV UNIVERSITY   (Israel)

ⁱ HEINRICH HEINE UNIVERSITY   (Germany)

Author keywords

[No Author keywords available]

Indexed keywords

ANTIVIRUS AGENT; CELL NUCLEUS RECEPTOR; HEPATOCYTE NUCLEAR FACTOR 4ALPHA; PEROXISOME PROLIFERATOR ACTIVATED RECEPTOR ALPHA; SOFOSBUVIR; CELL RECEPTOR;

APOPTOSIS; ARTICLE; CONTROLLED STUDY; DRUG METABOLISM; DRUG RESPONSE; GLYCOLYSIS; HEPATITIS C; HEPATITIS C VIRUS; HUMAN; HUMAN CELL; KETOGENESIS; LIFE CYCLE; LIPID OXIDATION; LIVER CELL; METABOLIC FLUX ANALYSIS; METABOLISM; NONHUMAN; PRIORITY JOURNAL; UPREGULATION; VIRUS ACTIVATION; VIRUS REPLICATION; DRUG EFFECTS; GROWTH, DEVELOPMENT AND AGING; HEPACIVIRUS; HOST PATHOGEN INTERACTION; VIROLOGY;

GLYCOLYSIS; HEPACIVIRUS; HEPATITIS C; HEPATOCYTES; HOST-PATHOGEN INTERACTIONS; HUMANS; RECEPTORS, CYTOPLASMIC AND NUCLEAR;

EID: 84990886692     PISSN: 15524450     EISSN: 15524469     Source Type: Journal    
DOI: 10.1038/nchembio.2193     Document Type: Article

References (60)

1. Munger, J., Bajad, S.U., Coller, H.A., Shenk, T. & Rabinowitz, J.D. Dynamics of the cellular metabolome during human cytomegalovirus infection. PLoS Pathog. 2, e132 (2006).
2. Munger, J. et al. Systems-level metabolic flux profiling identifies fatty acid synthesis as a target for antiviral therapy. Nat. Biotechnol. 26, 1179-1186 (2008).
3. Tam, V.C. et al. Lipidomic profiling of influenza infection identifies mediators that induce and resolve inflammation. Cell 154, 213-227 (2013).
4. Morita, M. et al. The lipid mediator protectin D1 inhibits influenza virus replication and improves severe influenza. Cell 153, 112-125 (2013).
5. Woodhouse, S.D. et al. Transcriptome sequencing, microarray, and proteomic analyses reveal cellular and metabolic impact of hepatitis C virus infection in vitro. Hepatology 52, 443-453 (2010).
6. Diamond, D.L. et al. Temporal proteome and lipidome profiles reveal hepatitis C virus-Associated reprogramming of hepatocellular metabolism and bioenergetics. PLoS Pathog. 6, e1000719 (2010).
7. Guidotti, L.G. & Chisari, F.V. Immunobiology and pathogenesis of viral hepatitis. Annu. Rev. Pathol. 1, 23-61 (2006).
8. Mihm, S. Hepatitis C virus, diabetes and steatosis: clinical evidence in favor of a linkage and role of genotypes. Dig. Dis. 28, 280-284 (2010).
9. Arrese, M., Riquelme, A. & Soza, A. Insulin resistance, hepatic steatosis and hepatitis C: a complex relationship with relevant clinical implications. Ann. Hepatol. 9, 112-118 (2010).
10. Ploss, A. et al. Persistent hepatitis C virus infection in microscale primary human hepatocyte cultures. Proc. Natl. Acad. Sci. USA 107, 3141-3145 (2010).
11. Ikeda, M. & Kato, N. Modulation of host metabolism as a target of new antivirals. Adv. Drug Deliv. Rev. 59, 1277-1289 (2007).
12. Chawla, A., Repa, J.J., Evans, R.M. & Mangelsdorf, D.J. Nuclear receptors and lipid physiology: opening the X-files. Science 294, 1866-1870 (2001).
13. Moxley, J.F. et al. Linking high-resolution metabolic flux phenotypes and transcriptional regulation in yeast modulated by the global regulator Gcn4p. Proc. Natl. Acad. Sci. USA 106, 6477-6482 (2009).
14. Kidambi, S. et al. Oxygen-mediated enhancement of primary hepatocyte metabolism, functional polarization, gene expression, and drug clearance. Proc. Natl. Acad. Sci. USA 106, 15714-15719 (2009).
15. Gardner, J.P. et al. L-SIGN (CD 209L) is a liver-specific capture receptor for hepatitis C virus. Proc. Natl. Acad. Sci. USA 100, 4498-4503 (2003).
16. Schaller, T. et al. Analysis of hepatitis C virus superinfection exclusion by using novel fluorochrome gene-tagged viral genomes. J. Virol. 81, 4591-4603 (2007).
17. Chan, C., Berthiaume, F., Lee, K. & Yarmush, M.L. Metabolic flux analysis of cultured hepatocytes exposed to plasma. Biotechnol. Bioeng. 81, 33-49 (2003).
18. Murakami, E. et al. Mechanism of activation of PSI-7851 and its diastereoisomer PSI-7977. J. Biol. Chem. 285, 34337-34347 (2010).
19. Liu, L. et al. Deregulated MYC expression induces dependence upon AMPK-related kinase 5. Nature 483, 608-612 (2012).
20. Ashburner, M. et al. Gene ontology: tool for the unification of biology. Nat. Genet. 25, 25-29 (2000).
21. Kanehisa, M. & Goto, S. KEGG: Kyoto encyclopedia of genes and genomes. Nucleic Acids Res. 28, 27-30 (2000).
22. Schmidt, D. et al. Five-vertebrate ChIP-seq reveals the evolutionary dynamics of transcription factor binding. Science 328, 1036-1040 (2010).
23. Horton, J.D. et al. Combined analysis of oligonucleotide microarray data from transgenic and knockout mice identifies direct SREBP target genes. Proc. Natl. Acad. Sci. USA 100, 12027-12032 (2003).
24. Kiselyuk, A. et al. HNF4? antagonists discovered by a high-throughput screen for modulators of the human insulin promoter. Chem. Biol. 19, 806-818 (2012).
25. Hertz, R., Sheena, V., Kalderon, B., Berman, I. & Bar-Tana, J. Suppression of hepatocyte nuclear factor-4? by acyl-CoA thioesters of hypolipidemic peroxisome proliferators. Biochem. Pharmacol. 61, 1057-1062 (2001).
26. Blight, K.J., Kolykhalov, A.A. & Rice, C.M. Efficient initiation of HCV RNA replication in cell culture. Science 290, 1972-1974 (2000).
27. Tanaka, N. et al. PPAR? activation is essential for HCV core protein-induced hepatic steatosis and hepatocellular carcinoma in mice. J. Clin. Invest. 118, 683-694 (2008).
28. Dharancy, S. et al. Impaired expression of the peroxisome proliferator-Activated receptor alpha during hepatitis C virus infection. Gastroenterology 128, 334-342 (2005).
29. Miyanari, Y. et al. The lipid droplet is an important organelle for hepatitis C virus production. Nat. Cell Biol. 9, 1089-1097 (2007).
30. Kapadia, S.B. & Chisari, F.V. Hepatitis C virus RNA replication is regulated by host geranylgeranylation and fatty acids. Proc. Natl. Acad. Sci. USA 102, 2561-2566 (2005).
31. Avior, Y. et al. Microbial-derived lithocholic acid and vitamin K2 drive the metabolic maturation of pluripotent stem cells-derived and fetal hepatocytes. Hepatology 62, 265-278 (2015).
32. Corey, K.E. et al. Hepatitis C virus infection and its clearance alter circulating lipids: implications for long-term follow-up. Hepatology 50, 1030-1037 (2009).
33. Avior, Y., Bomze, D., Ramon, O. & Nahmias, Y. Flavonoids as dietary regulators of nuclear receptor activity. Food Funct. 4, 831-844 (2013).
34. Wieland, S. et al. Simultaneous detection of hepatitis C virus and interferon stimulated gene expression in infected human liver. Hepatology 59, 2121-2130 (2014).
35. Kandathil, A.J. et al. Use of laser capture microdissection to map hepatitis C virus-positive hepatocytes in human liver. Gastroenterology 145, 1404-1413 (2013).
36. Merquiol, E. et al. HCV causes chronic endoplasmic reticulum stress leading to adaptation and interference with the unfolded protein response. PLoS One 6, e24660 (2011).
37. Okuda, M. et al. Mitochondrial injury, oxidative stress, and antioxidant gene expression are induced by hepatitis C virus core protein. Gastroenterology 122, 366-375 (2002).
38. Liu, J. et al. Enhancement of canonical Wnt/?-catenin signaling activity by HCV core protein promotes cell growth of hepatocellular carcinoma cells. PLoS One 6, e27496 (2011).
39. Yamagata, K. et al. Mutations in the hepatocyte nuclear factor-4? gene in maturity-onset diabetes of the young (MODY1). Nature 384, 458-460 (1996).
40. Qadri, I., Iwahashi, M., Kullak-Ublick, G.A. & Simon, F.R. Hepatocyte nuclear factor (HNF) 1 and HNF4 mediate hepatic multidrug resistance protein 2 up-regulation during hepatitis C virus gene expression. Mol. Pharmacol. 70, 627-636 (2006).
41. Matsui, C. et al. Hepatitis C virus infection suppresses GLUT2 gene expression via downregulation of hepatocyte nuclear factor 1?. J. Virol. 86, 12903-12911 (2012).
42. Vastag, L., Koyuncu, E., Grady, S.L., Shenk, T.E. & Rabinowitz, J.D. Divergent effects of human cytomegalovirus and herpes simplex virus-1 on cellular metabolism. PLoS Pathog. 7, e1002124 (2011).
43. Yamane, D. et al. Regulation of the hepatitis C virus RNA replicase by endogenous lipid peroxidation. Nat. Med. 20, 927-935 (2014).
44. Goldwasser, J. et al. Naringenin inhibits the assembly and long-term production of infectious hepatitis C virus particles through a PPAR-mediated mechanism. J. Hepatol. 55, 963-971 (2011).
45. Vacca, M. et al. Nuclear receptors in regenerating liver and hepatocellular carcinoma. Mol. Cell. Endocrinol. 368, 108-119 (2013).
46. Wang, C. et al. Identification of FBL2 as a geranylgeranylated cellular protein required for hepatitis C virus RNA replication. Mol. Cell 18, 425-434 (2005).
47. Nahmias, Y. et al. Apolipoprotein B-dependent hepatitis C virus secretion is inhibited by the grapefruit flavonoid naringenin. Hepatology 47, 1437-1445 (2008).
48. Teng, M.W. et al. An endogenous accelerator for viral gene expression confers a fitness advantage. Cell 151, 1569-1580 (2012).
49. Folmes, C.D.L. et al. Somatic oxidative bioenergetics transitions into pluripotency-dependent glycolysis to facilitate nuclear reprogramming. Cell Metab. 14, 264-271 (2011).
50. Fu, D. et al. Coordinated elevation of mitochondrial oxidative phosphorylation and autophagy help drive hepatocyte polarization. Proc. Natl. Acad. Sci. USA 110, 7288-7293 (2013).
51. Clarke, B., Wyatt, K.M. & McCormack, J.G. Ranolazine increases active pyruvate dehydrogenase in perfused normoxic rat hearts: evidence for an indirect mechanism. J. Mol. Cell. Cardiol. 28, 341-350 (1996).
52. Urizar, N.L. et al. A natural product that lowers cholesterol as an antagonist ligand for FXR. Science 296, 1703-1706 (2002).
53. Izamis, M.-L. et al. In situ metabolic flux analysis to quantify the liver metabolic response to experimental burn injury. Biotechnol. Bioeng. 108, 839-852 (2011).
54. Nahmias, Y. et al. A novel formulation of oxygen-carrying matrix enhances liver-specific function of cultured hepatocytes. FASEB J. 20, 2531-2533 (2006).
55. Lee, K., Berthiaume, F., Stephanopoulos, G.N., Yarmush, D.M. & Yarmush, M.L. Metabolic flux analysis of postburn hepatic hypermetabolism. Metab. Eng. 2, 312-327 (2000).
56. Chan, C., Berthiaume, F., Lee, K. & Yarmush, M.L. Metabolic flux analysis of hepatocyte function in hormone-And amino acid-supplemented plasma. Metab. Eng. 5, 1-15 (2003).
57. Zhang, J. et al. Measuring energy metabolism in cultured cells, including human pluripotent stem cells and differentiated cells. Nat. Protoc. 7, 1068-1085 (2012).
58. Mas, V.R. et al. Genes involved in viral carcinogenesis and tumor initiation in hepatitis C virus-induced hepatocellular carcinoma. Mol. Med. 15, 85-94 (2009).
59. Huang, W., Sherman, B.T. & Lempicki, R.A. Systematic and integrative analysis of large gene lists using DAVID bioinformatics resources. Nat. Protoc. 4, 44-57 (2009).
60. Miao, J., Fang, S., Bae, Y. & Kemper, J.K. Functional inhibitory cross-talk between constitutive androstane receptor and hepatic nuclear factor-4 in hepatic lipid/glucose metabolism is mediated by competition for binding to the DR1 motif and to the common coactivators, GRIP-1 and PGC-1?. J. Biol. Chem. 281, 14537-14546 (2006).