Hepatitis C virus infection activates an innate pathway involving IKK-α in lipogenesis and viral assembly

Nature Medicine

Volumn 19, Issue 6, 2013, Pages 722-729

  Li, Qisheng ^a   Pène, Véronique ^a   Krishnamurthy, Siddharth ^a   Cha, Helen ^a   Liang, T Jake ^a  

^a NATIONAL INSTITUTE OF DIABETES AND DIGESTIVE AND KIDNEY DISEASES   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

FAT DROPLET; I KAPPA B KINASE ALPHA; IMMUNOGLOBULIN ENHANCER BINDING PROTEIN; SMALL INTERFERING RNA; STEROL REGULATORY ELEMENT BINDING PROTEIN;

3' UNTRANSLATED REGION; ARTICLE; CHRONICITY; CONTROLLED STUDY; CYTOPLASM; ENZYME ANALYSIS; HEPATITIS C; INNATE IMMUNITY; LIPID METABOLISM; LIPOGENESIS; NONHUMAN; PRIORITY JOURNAL; PROTEIN FUNCTION; VIRUS GENOME;

3' UNTRANSLATED REGIONS; ACTIVE TRANSPORT, CELL NUCLEUS; DEAD-BOX RNA HELICASES; HEPATITIS C; HUMANS; I-KAPPA B KINASE; LIPOGENESIS; NF-KAPPA B; P300-CBP TRANSCRIPTION FACTORS; PHOSPHORYLATION; SIGNAL TRANSDUCTION; STEROL REGULATORY ELEMENT BINDING PROTEINS; VIRUS ASSEMBLY;

HEPATITIS C VIRUS;

EID: 84880290533     PISSN: 10788956     EISSN: 1546170X     Source Type: Journal    
DOI: 10.1038/nm.3190     Document Type: Article

References (55)

1. Liang, T.J., Rehermann, B., Seeff, L.B. & Hoofnagle, J.H. Pathogenesis, natural history, treatment, and prevention of hepatitis C. Ann. Intern. Med. 132, 296-305 (2000).
2. Liang, T.J. & Ghany, M.G. N. Engl. J. Med. 368, 1907-1917 (2013).
3. Rehermann, B. Hepatitis C virus versus innate and adaptive immune responses: a tale of coevolution and coexistence. J. Clin. Invest. 119, 1745-1754 (2009).
4. Syed, G.H., Amako, Y. & Siddiqui, A. Hepatitis C virus hijacks host lipid metabolism. Trends Endocrinol. Metab. 21, 33-40 (2010).
5. Herker, E. & Ott, M. Unique ties between hepatitis C virus replication and intracellular lipids. Trends Endocrinol. Metab. 22, 241-248 (2011).
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. Horton, J.D., Goldstein, J.L. & Brown, M.S. SREBPs: activators of the complete program of cholesterol and fatty acid synthesis in the liver. J. Clin. Invest. 109, 1125-1131 (2002).
8. Waris, G., Felmlee, D.J., Negro, F. & Siddiqui, A. Hepatitis C virus induces proteolytic cleavage of sterol regulatory element binding proteins and stimulates their phosphorylation via oxidative stress. J. Virol. 81, 8122-8130 (2007).
9. Lerat, H. et al. Hepatitis C virus proteins induce lipogenesis and defective triglyceride secretion in transgenic mice. J. Biol. Chem. 284, 33466-33474 (2009).
10. Bowie, A.G. & Unterholzner, L. Viral evasion and subversion of pattern-recognition receptor signalling. Nat. Rev. Immunol. 8, 911-922 (2008).
11. Hayden, M.S. & Ghosh, S. Shared principles in NF-κB signaling. Cell 132, 344-362 (2008).
12. Perkins, N.D. Integrating cell-signalling pathways with NF-κB and IKK function. Nat. Rev. Mol. Cell Biol. 8, 49-62 (2007).
13. Senftleben, U. et al. Activation by IKKα of a second, evolutionary conserved, NF-κB signaling pathway. Science 293, 1495-1499 (2001).
14. Pasparakis, M. Regulation of tissue homeostasis by NF-κB signalling: implications for inflammatory diseases. Nat. Rev. Immunol. 9, 778-788 (2009).
15. Anest, V. et al. A nucleosomal function for IκB kinase-α in NF-κB-dependent gene expression. Nature 423, 659-663 (2003).
16. Birbach, A. et al. Signaling molecules of the NF-κB pathway shuttle constitutively between cytoplasm and nucleus. J. Biol. Chem. 277, 10842-10851 (2002).
17. Yamamoto, Y., Verma, U.N., Prajapati, S., Kwak, Y.T. & Gaynor, R.B. Histone H3 phosphorylation by IKK-α is critical for cytokine-induced gene expression. Nature 423, 655-659 (2003).
18. Huang, W.C., Ju, T.K., Hung, M.C. & Chen, C.C. Phosphorylation of CBP by IKKα promotes cell growth by switching the binding preference of CBP from p53 to NF-κB. Mol. Cell 26, 75-87 (2007).
19. Li, Q. et al. A genome-wide genetic screen for host factors required for hepatitis C virus propagation. Proc. Natl. Acad. Sci. USA 106, 16410-16415 (2009).
20. Zandi, E., Rothwarf, D.M., Delhase, M., Hayakawa, M. & Karin, M. The IκB kinase complex (IKK) contains two kinase subunits, IKKα and IKKβ, necessary for IκB phosphorylation and NF-κB activation. Cell 91, 243-252 (1997).
21. Akazawa, D. et al. CD81 expression is important for the permissiveness of Huh7 cell clones for heterogeneous hepatitis C virus infection. J. Virol. 81, 5036-5045 (2007).
22. Miyanari, Y. et al. The lipid droplet is an important organelle for hepatitis C virus production. Nat. Cell Biol. 9, 1089-1097 (2007).
23. Herker, E. et al. Efficient hepatitis C virus particle formation requires diacylglycerol acyltransferase-1. Nat. Med. 16, 1295-1298 (2010).
24. McLauchlan, J. Lipid droplets and hepatitis C virus infection. Biochim. Biophys. Acta 1791, 552-559 (2009).
25. Saito, T., Owen, D.M., Jiang, F., Marcotrigiano, J. & Gale, M. Jr. Innate immunity induced by composition-dependent RIG-I recognition of hepatitis C virus RNA. Nature 454, 523-527 (2008).
26. Rothenfusser, S. et al. The RNA helicase Lgp2 inhibits TLR-independent sensing of viral replication by retinoic acid-inducible gene-I. J. Immunol. 175, 5260-5268 (2005).
27. Zhang, Z. et al. DDX1, DDX21, and DHX36 helicases form a complex with the adaptor molecule TRIF to sense dsRNA in dendritic cells. Immunity 34, 866-878 (2011).
28. Oshiumi, H., Sakai, K., Matsumoto, M. & Seya, T. DEAD/H BOX 3 (DDX3) helicase binds the RIG-I adaptor IPS-1 to up-regulate IFN-β-inducing potential. Eur. J. Immunol. 40, 940-948 (2010).
29. Schröder, M., Baran, M. & Bowie, A.G. Viral targeting of DEAD box protein 3 reveals its role in TBK1/IKKε-mediated IRF activation. EMBO J. 27, 2147-2157 (2008).
30. Ariumi, Y. et al. DDX3 DEAD-box RNA helicase is required for hepatitis C virus RNA replication. J. Virol. 81, 13922-13926 (2007).
31. Randall, G. et al. Cellular cofactors affecting hepatitis C virus infection and replication. Proc. Natl. Acad. Sci. USA 104, 12884-12889 (2007).
32. Oshiumi, H. et al. Hepatitis C virus core protein abrogates the DDX3 function that enhances IPS-1-mediated IFN-β induction. PLoS ONE 5, e14258 (2010).
33. Angus, A.G. et al. Requirement of cellular DDX3 for hepatitis C virus replication is unrelated to its interaction with the viral core protein. J. Gen. Virol. 91, 122-132 (2010).
34. Reed, B.D., Charos, A.E., Szekely, A.M., Weissman, S.M. & Snyder, M. Genome-wide occupancy of SREBP1 and its partners NFY and SP1 reveals novel functional roles and combinatorial regulation of distinct classes of genes. PLoS Genet. 4, e1000133 (2008).
35. Ericsson, J. & Edwards, P.A. CBP is required for sterol-regulated and sterol regulatory element-binding protein-regulated transcription. J. Biol. Chem. 273, 17865-17870 (1998).
36. Oliner, J.D., Andresen, J.M., Hansen, S.K., Zhou, S. & Tjian, R. SREBP transcriptional activity is mediated through an interaction with the CREB-binding protein. Genes Dev. 10, 2903-2911 (1996).
37. Giandomenico, V., Simonsson, M., Gronroos, E. & Ericsson, J. Coactivator-dependent acetylation stabilizes members of the SREBP family of transcription factors. Mol. Cell Biol. 23, 2587-2599 (2003).
38. Brass, A.L. et al. Identification of host proteins required for HIV infection through a functional genomic screen. Science 319, 921-926 (2008).
39. Sessions, O.M. et al. Discovery of insect and human dengue virus host factors. Nature 458, 1047-1050 (2009).
40. Krishnan, M.N. et al. RNA interference screen for human genes associated with West Nile virus infection. Nature 455, 242-245 (2008).
41. Brass, A.L. et al. The IFITM proteins mediate cellular resistance to influenza A H1N1 virus, West Nile virus, and dengue virus. Cell 139, 1243-1254 (2009).
42. Heaton, N.S. & Randall, G. Dengue virus-induced autophagy regulates lipid metabolism. Cell Host Microbe 8, 422-432 (2010).
43. Mackenzie, J.M., Khromykh, A.A. & Parton, R.G. Cholesterol manipulation by West Nile virus perturbs the cellular immune response. Cell Host Microbe 2, 229-239 (2007).
44. Hsu, N.Y. et al. Viral reorganization of the secretory pathway generates distinct organelles for RNA replication. Cell 141, 799-811 (2010).
45. Farese, R.V. Jr. & Walther, T.C. Lipid droplets finally get a little R-E-S-P-E-C-T. Cell 139, 855-860 (2009).
46. Asselah, T., Rubbia-Brandt, L., Marcellin, P. & Negro, F. Steatosis in chronic hepatitis C: why does it really matter? Gut 55, 123-130 (2006).
47. Cai, D. et al. Local and systemic insulin resistance resulting from hepatic activation of IKK-β and NF-κB. Nat. Med. 11, 183-190 (2005).
48. Yuan, M. et al. Reversal of obesity- and diet-induced insulin resistance with salicylates or targeted disruption of Ikkβ. Science 293, 1673-1677 (2001).
49. Arkan, M.C. et al. IKK-β links inflammation to obesity-induced insulin resistance. Nat. Med. 11, 191-198 (2005).
50. Zhang, X. et al. Hypothalamic IKKβ/NF-κB and ER stress link overnutrition to energy imbalance and obesity. Cell 135, 61-73 (2008).
51. Romeo, S. et al. Genetic variation in PNPLA3 confers susceptibility to nonalcoholic fatty liver disease. Nat. Genet. 40, 1461-1465 (2008).
52. Hotamisligil, G.S. Inflammation and metabolic disorders. Nature 444, 860-867 (2006).
53. Baker, R.G., Hayden, M.S. & Ghosh, S. NF-κB, inflammation, and metabolic disease. Cell Metab. 13, 11-22 (2011).
54. 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).
55. Feld, J.J. et al. Hepatic gene expression during treatment with peginterferon and ribavirin: identifying molecular pathways for treatment response. Hepatology 46, 1548-1563 (2007).