Interaction of the hepatitis C virus (HCV) core with cellular genes in the development of HCV-induced steatosis

Archives of Virology

Volumn 155, Issue 11, 2010, Pages 1735-1753

  Khan, Mahwish ^a   Jahan, Shah ^a   Khaliq, Saba ^a   Ijaz, Bushra ^a   Ahmad, Waqar ^a   Samreen, Baila ^a   Hassan, Sajida ^a  

^a UNIVERSITY OF THE PUNJAB   (Pakistan)

Author keywords

[No Author keywords available]

Indexed keywords

CORE PROTEIN;

FATTY LIVER; GENE EXPRESSION REGULATION; GENETIC POLYMORPHISM; GENETICS; HEPATITIS C; HEPATITIS C VIRUS; HUMAN; METABOLISM; PATHOLOGY; REVIEW; VIROLOGY;

FATTY LIVER; GENE EXPRESSION REGULATION, VIRAL; HEPACIVIRUS; HEPATITIS C, CHRONIC; HUMANS; POLYMORPHISM, GENETIC; VIRAL CORE PROTEINS;

HEPATITIS C VIRUS;

EID: 78149410401     PISSN: 03048608     EISSN: None     Source Type: Journal    
DOI: 10.1007/s00705-010-0797-7     Document Type: Review

References (217)

1. Abid K, Pazienza V, de Gottardi A, Rubbia-Brandt L, Conne B, Pugnale P, Rossi C, Mangia A, Negro F (2005) An in vitro model of hepatitis C virus genotype 3a-associated triglycerides accumulation. J Hepatol 42: 744-751.
2. Abu-Elheiga L, Brinkley WR, Zhong L, Chirala SS, Woldegiorgis G, Wakil SJ (2000) The subcellular localization of acetyl-CoA carboxylase 2. Proc Natl Acad Sci USA 97: 1444-1449.
3. Adinolfi LE, Ingrosso D, Cesaro G, Cimmino A, D'Anto M, Capasso R, Zappia V, Ruggiero G (2005) Hyperhomocysteinemia and the MTHFR C677T polymorphism promote steatosis and fibrosis in chronic hepatitis C patients. Hepatology 41: 995-1003.
4. Agnello V, Abel G, Elfahal M, Knight GB, Zhang QX (1999) Hepatitis C virus and other flaviviridae viruses enter cells via low density lipoprotein receptor. Proc Natl Acad Sci USA 96: 12766-12771.
5. Aizaki H, Lee KJ, Sung VM, Ishiko H, Lai MM (2004) Characterization of the hepatitis C virus RNA replication complex associated with lipid rafts. Virology 324: 450-461.
6. Alter MJ (2007) Epidemiology of hepatitis C virus infection. World J Gastroenterol 13: 2436-2441.
7. Andre P, Perlemuter G, Budkowska A, Brechot C, Lotteau V (2005) Hepatitis C virus particles and lipoprotein metabolism. Semin Liver Dis 25: 93-104.
8. Appel N, Zayas M, Miller S, Krijnse-Locker J, Schaller T, Friebe P, Kallis S, Engel U, Bartenschlager R (2008) Essential role of domain III of nonstructural protein 5A for hepatitis C virus infectious particle assembly. PLoS Pathog 4: e1000035.
9. Assifi MM, Suchankova G, Constant S, Prentki M, Saha AK, Ruderman NB (2005) AMP-activated protein kinase and coordination of hepatic fatty acid metabolism of starved/carbohydrate-refed rats. Am J Physiol Endocrinol Metab 289: E794-E800.
10. Aytug S, Reich D, Sapiro LE, Bernstein D, Begum N (2003) Impaired IRS-1/PI3-kinase signaling in patients with HCV: a mechanism for increased prevalence of type 2 diabetes. Hepatology 38: 1384-1392.
11. Bach N, Thung SN, Schaffner F (1992) The histological features of chronic hepatitis C and autoimmune chronic hepatitis: a comparative analysis. Hepatology 15: 572-577.
12. Banerjee S, Saito K, Ait-Goughoulte M, Meyer K, Ray RB, Ray R (2008) Hepatitis C virus core protein upregulates serine phosphorylation of insulin receptor substrate-1 and impairs the downstream akt/protein kinase B signaling pathway for insulin resistance. J Virol 82: 2606-2612.
13. Bantel H, Schulze-Osthoff K (2003) Apoptosis in hepatitis C virus infection. Cell Death Differ 10(Suppl 1): S48-S58.
14. Barba G, Harper F, Harada T, Kohara M, Goulinet S, Matsuura Y, Eder G, Schaff Z, Chapman MJ, Miyamura T, Brechot C (1997) Hepatitis C virus core protein shows a cytoplasmic localization and associates to cellular lipid storage droplets. Proc Natl Acad Sci USA 94: 1200-1205.
15. Bartenschlager R, Lohmann V (2001) Novel cell culture systems for the hepatitis C virus. Antiviral Res 52: 1-17.
16. Bartenschlager R, Sparacio S (2007) Hepatitis C virus molecular clones and their replication capacity in vivo and in cell culture. Virus Res 127: 195-207.
17. Beltowski J (2003) Adiponectin and resistin-new hormones of white adipose tissue. Med Sci Monit 9: RA55-RA61.
18. Benali-Furet NL, Chami M, Houel L, De Giorgi F, Vernejoul F, Lagorce D, Buscail L, Bartenschlager R, Ichas F, Rizzuto R, Paterlini-Brechot P (2005) Hepatitis C virus core triggers apoptosis in liver cells by inducing ER stress and ER calcium depletion. Oncogene 24: 4921-4933.
19. Benedicto I, Molina-Jimenez F, Barreiro O, Maldonado-Rodriguez A, Prieto J, Moreno-Otero R, Aldabe R, Lopez-Cabrera M, Majano PL (2008) Hepatitis C virus envelope components alter localization of hepatocyte tight junction-associated proteins and promote occludin retention in the endoplasmic reticulum. Hepatology 48: 1044-1053.
20. Bevan P (2001) Insulin signalling. J Cell Sci 114: 1429-1430.
21. Bieche I, Asselah T, Laurendeau I, Vidaud D, Degot C, Paradis V, Bedossa P, Valla DC, Marcellin P, Vidaud M (2005) Molecular profiling of early stage liver fibrosis in patients with chronic hepatitis C virus infection. Virology 332: 130-144.
22. Bigger CB, Guerra B, Brasky KM, Hubbard G, Beard MR, Luxon BA, Lemon SM, Lanford RE (2004) Intrahepatic gene expression during chronic hepatitis C virus infection in chimpanzees. J Virol 78: 13779-13792.
23. Boulant S, Targett-Adams P, McLauchlan J (2007) Disrupting the association of hepatitis C virus core protein with lipid droplets correlates with a loss in production of infectious virus. J Gen Virol 88: 2204-2213.
24. Brown MS, Goldstein JL (1986) A receptor-mediated pathway for cholesterol homeostasis. Science 232: 34-47.
25. Brown MS, Goldstein JL (1997) The SREBP pathway: regulation of cholesterol metabolism by proteolysis of a membrane-bound transcription factor. Cell 89: 331-340.
26. Browning JD, Horton JD (2004) Molecular mediators of hepatic steatosis and liver injury. J Clin Invest 114: 147-152.
27. Bukh J (2004) A critical role for the chimpanzee model in the study of hepatitis C. Hepatology 39: 1469-1475.
28. Chandler CE, Wilder DE, Pettini JL, Savoy YE, Petras SF, Chang G, Vincent J, Harwood HJ Jr (2003) CP-346086: an MTP inhibitor that lowers plasma cholesterol and triglycerides in experimental animals and in humans. J Lipid Res 44: 1887-1901.
29. Chang KS, Jiang J, Cai Z, Luo G (2007) Human apolipoprotein e is required for infectivity and production of hepatitis C virus in cell culture. J Virol 81: 13783-13793.
30. Cheng Y, Dharancy S, Malapel M, Desreumaux P (2005) Hepatitis C virus infection down-regulates the expression of peroxisome proliferator-activated receptor alpha and carnitine palmitoyl acyl-CoA transferase 1A. World J Gastroenterol 11: 7591-7596.
31. Christen V, Treves S, Duong FH, Heim MH (2007) Activation of endoplasmic reticulum stress response by hepatitis viruses up-regulates protein phosphatase 2A. Hepatology 46: 558-565.
32. Chung NS, Wasan KM (2004) Potential role of the low-density lipoprotein receptor family as mediators of cellular drug uptake. Adv Drug Deliv Rev 56: 1315-1334.
33. Ciccaglione AR, Marcantonio C, Tritarelli E, Equestre M, Vendittelli F, Costantino A, Geraci A, Rapicetta M (2007) Activation of the ER stress gene gadd153 by hepatitis C virus sensitizes cells to oxidant injury. Virus Res 126: 128-138.
34. Cuchel M, Bloedon LT, Szapary PO, Kolansky DM, Wolfe ML, Sarkis A, Millar JS, Ikewaki K, Siegelman ES, Gregg RE, Rader DJ (2007) Inhibition of microsomal triglyceride transfer protein in familial hypercholesterolemia. N Engl J Med 356: 148-156.
35. de Gottardi A, Pazienza V, Pugnale P, Bruttin F, Rubbia-Brandt L, Juge-Aubry CE, Meier CA, Hadengue A, Negro F (2006) Peroxisome proliferator-activated receptor-alpha and -gamma mRNA levels are reduced in chronic hepatitis C with steatosis and genotype 3 infection. Aliment Pharmacol Ther 23: 107-114.
36. Deng L, Adachi T, Kitayama K, Bungyoku Y, Kitazawa S, Ishido S, Shoji I, Hotta H (2008) Hepatitis C virus infection induces apoptosis through a Bax-triggered, mitochondrion-mediated, caspase 3-dependent pathway. J Virol 82: 10375-10385.
37. Dharancy S, Malapel M, Perlemuter G, Roskams T, Cheng Y, Dubuquoy L, Podevin P, Conti F, Canva V, Philippe D, Gambiez L, Mathurin P, Paris JC, Schoonjans K, Calmus Y, Pol S, Auwerx J, Desreumaux P (2005) Impaired expression of the peroxisome proliferator-activated receptor alpha during hepatitis C virus infection. Gastroenterology 128: 334-342.
38. Diez JJ, Iglesias P (2003) The role of the novel adipocyte-derived hormone adiponectin in human disease. Eur J Endocrinol 148: 293-300.
39. Dimcheff DE, Faasse MA, McAtee FJ, Portis JL (2004) Endoplasmic reticulum (ER) stress induced by a neurovirulent mouse retrovirus is associated with prolonged BiP binding and retention of a viral protein in the ER. J Biol Chem 279: 33782-33790.
40. Durante-Mangoni E, Zampino R, Marrone A, Tripodi MF, Rinaldi L, Restivo L, Cioffi M, Ruggiero G, Adinolfi LE (2006) Hepatic steatosis and insulin resistance are associated with serum imbalance of adiponectin/tumour necrosis factor-alpha in chronic hepatitis C patients. Aliment Pharmacol Ther 24: 1349-1357.
41. El-Serag HB, Tran T, Everhart JE (2004) Diabetes increases the risk of chronic liver disease and hepatocellular carcinoma. Gastroenterology 126: 460-468.
42. Eugene JY, Hu K-Q (2006) HCV infection and hepatic steatosis. Int J Med Sci 3: 53-56.
43. Feitelson MA (2002) Hepatitis C virus: from laboratory to clinic. Cambridge University Press, New York.
44. Foretz M, Guichard C, Ferre P, Foufelle F (1999) Sterol regulatory element binding protein-1c is a major mediator of insulin action on the hepatic expression of glucokinase and lipogenesis-related genes. Proc Natl Acad Sci USA 96: 12737-12742.
45. Fukasawa M, Tanaka Y, Sato S, Ono Y, Nitahara-Kasahara Y, Suzuki T, Miyamura T, Hanada K, Nishijima M (2006) Enhancement of de novo fatty acid biosynthesis in hepatic cell line Huh7 expressing hepatitis C virus core protein. Biol Pharm Bull 29: 1958-1961.
46. Furuta K, Sato S, Yamauchi T, Kakumu S (2008) Changes in intrahepatic gene expression profiles from chronic hepatitis to hepatocellular carcinoma in patients with hepatitis C virus infection. Hepatol Res 38: 673-682.
47. Gastaminza P, Cheng G, Wieland S, Zhong J, Liao W, Chisari FV (2008) Cellular determinants of hepatitis C virus assembly, maturation, degradation, and secretion. J Virol 82: 2120-2129.
48. Gerber MA, Krawczynski K, Alter MJ, Sampliner RE, Margolis HS (1992) Histopathology of community acquired chronic hepatitis C. The Sentinel Counties Chronic Non-A, Non-B Hepatitis Study Team. Mod Pathol 5: 483-486.
49. Gibbons GF, Wiggins D, Brown AM, Hebbachi AM (2004) Synthesis and function of hepatic very-low-density lipoprotein. Biochem Soc Trans 32: 59-64.
50. Goldstein BJ, Scalia R (2004) Adiponectin: a novel adipokine linking adipocytes and vascular function. J Clin Endocrinol Metab 89: 2563-2568.
51. Goldstein JL, Brown MS (1990) Regulation of the mevalonate pathway. Nature 343: 425-430.
52. Gopal K, Johnson TC, Gopal S, Walfish A, Bang CT, Suwandhi P, Pena-Sahdala HN, Clain DJ, Bodenheimer HC Jr, Min AD (2006) Correlation between beta-lipoprotein levels and outcome of hepatitis C treatment. Hepatology 44: 335-340.
53. Halse R, Pearson SL, McCormack JG, Yeaman SJ, Taylor R (2001) Effects of tumor necrosis factor-alpha on insulin action in cultured human muscle cells. Diabetes 50: 1102-1109.
54. Hardie DG (2003) Minireview: the AMP-activated protein kinase cascade: the key sensor of cellular energy status. Endocrinology 144: 5179-5183.
55. Hardie DG (2004) The AMP-activated protein kinase pathway-new players upstream and downstream. J Cell Sci 117: 5479-5487.
56. Hezode C, Roudot-Thoraval F, Zafrani ES, Dhumeaux D, Pawlotsky JM (2004) Different mechanisms of steatosis in hepatitis C virus genotypes 1 and 3 infections. J Viral Hepat 11: 455-458.
57. Higuchi N, Kato M, Shundo Y, Tajiri H, Tanaka M, Yamashita N, Kohjima M, Kotoh K, Nakamuta M, Takayanagi R, Enjoji M (2008) Liver X receptor in cooperation with SREBP-1c is a major lipid synthesis regulator in nonalcoholic fatty liver disease. Hepatol Res 38: 1122-1129.
58. Hoofnagle JH (2002) Course and outcome of hepatitis C. Hepatology 36: S21-S29.
59. Hope RG, McLauchlan J (2000) Sequence motifs required for lipid droplet association and protein stability are unique to the hepatitis C virus core protein. J Gen Virol 81: 1913-1925.
60. Horscroft N, Lai VC, Cheney W, Yao N, Wu JZ, Hong Z, Zhong W (2005) Replicon cell culture system as a valuable tool in antiviral drug discovery against hepatitis C virus. Antivir Chem Chemother 16: 1-12.
61. Horton JD, Goldstein JL, Brown MS (2002) SREBPs: activators of the complete program of cholesterol and fatty acid synthesis in the liver. J Clin Invest 109: 1125-1131.
62. Horton JD, Shah NA, Warrington JA, Anderson NN, Park SW, Brown MS, Goldstein JL (2003) Combined analysis of oligonucleotide microarray data from transgenic and knockout mice identifies direct SREBP target genes. Proc Natl Acad Sci USA 100: 12027-12032.
63. Hotta K, Funahashi T, Arita Y, Takahashi M, Matsuda M, Okamoto Y, Iwahashi H, Kuriyama H, Ouchi N, Maeda K, Nishida M, Kihara S, Sakai N, Nakajima T, Hasegawa K, Muraguchi M, Ohmoto Y, Nakamura T, Yamashita S, Hanafusa T, Matsuzawa Y (2000) Plasma concentrations of a novel, adipose-specific protein, adiponectin, in type 2 diabetic patients. Arterioscler Thromb Vasc Biol 20: 1595-1599.
64. Hourioux C, Patient R, Morin A, Blanchard E, Moreau A, Trassard S, Giraudeau B, Roingeard P (2007) The genotype 3-specific hepatitis C virus core protein residue phenylalanine 164 increases steatosis in an in vitro cellular model. Gut 56: 1302-1308.
65. Huang H, Sun F, Owen DM, Li W, Chen Y, Gale M Jr, Ye J (2007) Hepatitis C virus production by human hepatocytes dependent on assembly and secretion of very low-density lipoproteins. Proc Natl Acad Sci USA 104: 5848-5853.
66. Hui JM, Hodge A, Farrell GC, Kench JG, Kriketos A, George J (2004) Beyond insulin resistance in NASH: TNF-alpha or adiponectin? Hepatology 40: 46-54.
67. Hussy P, Langen H, Mous J, Jacobsen H (1996) Hepatitis C virus core protein: carboxy-terminal boundaries of two processed species suggest cleavage by a signal peptide peptidase. Virology 224: 93-104.
68. Ikeda M, Abe K, Yamada M, Dansako H, Naka K, Kato N (2006) Different anti-HCV profiles of statins and their potential for combination therapy with interferon. Hepatology 44: 117-125.
69. Ilan E, Arazi J, Nussbaum O, Zauberman A, Eren R, Lubin I, Neville L, Ben-Moshe O, Kischitzky A, Litchi A, Margalit I, Gopher J, Mounir S, Cai W, Daudi N, Eid A, Jurim O, Czerniak A, Galun E, Dagan S (2002) The hepatitis C virus (HCV)-Trimera mouse: a model for evaluation of agents against HCV. J Infect Dis 185: 153-161.
70. Im SS, Kwon SK, Kim TH, Kim HI, Ahn YH (2007) Regulation of glucose transporter type 4 isoform gene expression in muscle and adipocytes. IUBMB Life 59: 134-145.
71. Iwaki M, Matsuda M, Maeda N, Funahashi T, Matsuzawa Y, Makishima M, Shimomura I (2003) Induction of adiponectin, a fat-derived antidiabetic and antiatherogenic factor, by nuclear receptors. Diabetes 52: 1655-1663.
72. Jackel-Cram C, Babiuk LA, Liu Q (2007) Up-regulation of fatty acid synthase promoter by hepatitis C virus core protein: genotype-3a core has a stronger effect than genotype-1b core. J Hepatol 46: 999-1008.
73. Jhaveri R, McHutchison J, Patel K, Qiang G, Diehl AM (2008) Specific polymorphisms in hepatitis C virus genotype 3 core protein associated with intracellular lipid accumulation. J Infect Dis 197: 283-291.
74. Ji C (2008) Dissection of endoplasmic reticulum stress signaling in alcoholic and non-alcoholic liver injury. J Gastroenterol Hepatol 23(Suppl 1): S16-S24.
75. Jonsson JR, Moschen AR, Hickman IJ, Richardson MM, Kaser S, Clouston AD, Powell EE, Tilg H (2005) Adiponectin and its receptors in patients with chronic hepatitis C. J Hepatol 43: 929-936.
76. Kaiser S (1998) Cell volume regulates liver phosphoenolpyruvate carboxykinase and fructose-1, 6-bisphosphatase genes. Am J Physiol 274: G509-G517.
77. Kapadia SB, Chisari FV (2005) Hepatitis C virus RNA replication is regulated by host geranylgeranylation and fatty acids. Proc Natl Acad Sci USA 102: 2561-2566.
78. Kapadia SB, Barth H, Baumert T, McKeating JA, Chisari FV (2007) Initiation of hepatitis C virus infection is dependent on cholesterol and cooperativity between CD81 and scavenger receptor B type I. J Virol 81: 374-383.
79. Kawaguchi T, Yoshida T, Harada M, Hisamoto T, Nagao Y, Ide T, Taniguchi E, Kumemura H, Hanada S, Maeyama M, Baba S, Koga H, Kumashiro R, Ueno T, Ogata H, Yoshimura A, Sata M (2004) Hepatitis C virus down-regulates insulin receptor substrates 1 and 2 through up-regulation of suppressor of cytokine signaling 3. Am J Pathol 165: 1499-1508.
80. Kersten S, Seydoux J, Peters JM, Gonzalez FJ, Desvergne B, Wahli W (1999) Peroxisome proliferator-activated receptor alpha mediates the adaptive response to fasting. J Clin Invest 103: 1489-1498.
81. Kim K, Kim KH, Ha E, Park JY, Sakamoto N, Cheong J (2009) Hepatitis C virus NS5A protein increases hepatic lipid accumulation via induction of activation and expression of PPARgamma. FEBS Lett 583: 2720-2726.
82. Kneteman NM, Weiner AJ, O'Connell J, Collett M, Gao T, Aukerman L, Kovelsky R, Ni ZJ, Zhu Q, Hashash A, Kline J, Hsi B, Schiller D, Douglas D, Tyrrell DL, Mercer DF (2006) Anti-HCV therapies in chimeric scid-Alb/uPA mice parallel outcomes in human clinical application. Hepatology 43: 1346-1353.
83. Knobler H, Schattner A (2005) TNF-{alpha}, chronic hepatitis C and diabetes: a novel triad. Qjm 98: 1-6.
84. Kohjima M, Higuchi N, Kato M, Kotoh K, Yoshimoto T, Fujino T, Yada M, Yada R, Harada N, Enjoji M, Takayanagi R, Nakamuta M (2008) SREBP-1c, regulated by the insulin and AMPK signaling pathways, plays a role in nonalcoholic fatty liver disease. Int J Mol Med 21: 507-511.
85. Kolykhalov AA, Agapov EV, Blight KJ, Mihalik K, Feinstone SM, Rice CM (1997) Transmission of hepatitis C by intrahepatic inoculation with transcribed RNA. Science 277: 570-574.
86. Korenaga M, Wang T, Li Y, Showalter LA, Chan T, Sun J, Weinman SA (2005) Hepatitis C virus core protein inhibits mitochondrial electron transport and increases reactive oxygen species (ROS) production. J Biol Chem 280: 37481-37488.
87. Kuipers F, Jong MC, Lin Y, Eck M, Havinga R, Bloks V, Verkade HJ, Hofker MH, Moshage H, Berkel TJ, Vonk RJ, Havekes LM (1997) Impaired secretion of very low density lipoprotein-triglycerides by apolipoprotein E- deficient mouse hepatocytes. J Clin Invest 100: 2915-2922.
88. Kumar D, Farrell GC, Fung C, George J (2002) Hepatitis C virus genotype 3 is cytopathic to hepatocytes: Reversal of hepatic steatosis after sustained therapeutic response. Hepatology 36: 1266-1272.
89. Labonte P, Begley S, Guevin C, Asselin MC, Nassoury N, Mayer G, Prat A, Seidah NG (2009) PCSK9 impedes hepatitis C virus infection in vitro and modulates liver CD81 expression. Hepatology 50: 17-24.
90. Leone TC, Weinheimer CJ, Kelly DP (1999) A critical role for the peroxisome proliferator-activated receptor alpha (PPARalpha) in the cellular fasting response: the PPARalpha-null mouse as a model of fatty acid oxidation disorders. Proc Natl Acad Sci USA 96: 7473-7478.
91. Lerat H, Honda M, Beard MR, Loesch K, Sun J, Yang Y, Okuda M, Gosert R, Xiao SY, Weinman SA, Lemon SM (2002) Steatosis and liver cancer in transgenic mice expressing the structural and nonstructural proteins of hepatitis C virus. Gastroenterology 122: 352-365.
92. Lerat H, Kammoun HL, Hainault I, Merour E, Higgs MR, Callens C, Lemon SM, Foufelle F, Pawlotsky JM (2009) Hepatitis C virus proteins induce lipogenesis and defective triglyceride secretion in transgenic mice. J Biol Chem 284: 33466-33474.
93. Lindenbach BD, Evans MJ, Syder AJ, Wolk B, Tellinghuisen TL, Liu CC, Maruyama T, Hynes RO, Burton DR, McKeating JA, Rice CM (2005) Complete replication of hepatitis C virus in cell culture. Science 309: 623-626.
94. Liu N, Kuang X, Kim HT, Stoica G, Qiang W, Scofield VL, Wong PK (2004) Possible involvement of both endoplasmic reticulum- and mitochondria-dependent pathways in MoMuLV-ts1-induced apoptosis in astrocytes. J Neurovirol 10: 189-198.
95. Lohmann V, Korner F, Koch J, Herian U, Theilmann L, Bartenschlager R (1999) Replication of subgenomic hepatitis C virus RNAs in a hepatoma cell line. Science 285: 110-113.
96. Lonardo A, Loria P, Adinolfi LE, Carulli N, Ruggiero G (2006) Hepatitis C and steatosis: a reappraisal. J Viral Hepat 13: 73-80.
97. Maeda K, Okubo K, Shimomura I, Funahashi T, Matsuzawa Y, Matsubara K (1996) cDNA cloning and expression of a novel adipose specific collagen-like factor, apM1 (AdiPose Most abundant Gene transcript 1). Biochem Biophys Res Commun 221: 286-289.
98. Magnusson B, Asp L, Bostrom P, Ruiz M, Stillemark-Billton P, Linden D, Boren J, Olofsson SO (2006) Adipocyte differentiation-related protein promotes fatty acid storage in cytosolic triglycerides and inhibits secretion of very low-density lipoproteins. Arterioscler Thromb Vasc Biol 26: 1566-1571.
99. Major ME, Dahari H, Mihalik K, Puig M, Rice CM, Neumann AU, Feinstone SM (2004) Hepatitis C virus kinetics and host responses associated with disease and outcome of infection in chimpanzees. Hepatology 39: 1709-1720.
100. Mangelsdorf DJ, Evans RM (1995) The RXR heterodimers and orphan receptors. Cell 83: 841-850.
101. Mangelsdorf DJ, Thummel C, Beato M, Herrlich P, Schutz G, Umesono K, Blumberg B, Kastner P, Mark M, Chambon P, Evans RM (1995) The nuclear receptor superfamily: the second decade. Cell 83: 835-839.
102. Marchesini G, Marzocchi R, Agostini F, Bugianesi E (2005) Nonalcoholic fatty liver disease and the metabolic syndrome. Curr Opin Lipidol 16: 421-427.
103. Masaki T, Suzuki R, Murakami K, Aizaki H, Ishii K, Murayama A, Date T, Matsuura Y, Miyamura T, Wakita T, Suzuki T (2008) Interaction of hepatitis C virus nonstructural protein 5A with core protein is critical for the production of infectious virus particles. J Virol 82: 7964-7976.
104. McGarry JD, Brown NF (1997) The mitochondrial carnitine palmitoyltransferase system. From concept to molecular analysis. Eur J Biochem 244: 1-14.
105. McLauchlan J, Lemberg MK, Hope G, Martoglio B (2002) Intramembrane proteolysis promotes trafficking of hepatitis C virus core protein to lipid droplets. EMBO J 21: 3980-3988.
106. Mercer DF, Schiller DE, Elliott JF, Douglas DN, Hao C, Rinfret A, Addison WR, Fischer KP, Churchill TA, Lakey JR, Tyrrell DL, Kneteman NM (2001) Hepatitis C virus replication in mice with chimeric human livers. Nat Med 7: 927-933.
107. Mihm S, Fayyazi A, Hartmann H, Ramadori G (1997) Analysis of histopathological manifestations of chronic hepatitis C virus infection with respect to virus genotype. Hepatology 25: 735-739.
108. Mirandola S, Realdon S, Iqbal J, Gerotto M, Dal Pero F, Bortoletto G, Marcolongo M, Vario A, Datz C, Hussain MM, Alberti A (2006) Liver microsomal triglyceride transfer protein is involved in hepatitis C liver steatosis. Gastroenterology 130: 1661-1669.
109. Miyanari Y, Atsuzawa K, Usuda N, Watashi K, Hishiki T, Zayas M, Bartenschlager R, Wakita T, Hijikata M, Shimotohno K (2007) The lipid droplet is an important organelle for hepatitis C virus production. Nat Cell Biol 9: 1089-1097.
110. Molina S, Castet V, Fournier-Wirth C, Pichard-Garcia L, Avner R, Harats D, Roitelman J, Barbaras R, Graber P, Ghersa P, Smolarsky M, Funaro A, Malavasi F, Larrey D, Coste J, Fabre JM, Sa-Cunha A, Maurel P (2007) The low-density lipoprotein receptor plays a role in the infection of primary human hepatocytes by hepatitis C virus. J Hepatol 46: 411-419.
111. Monazahian M, Bohme I, Bonk S, Koch A, Scholz C, Grethe S, Thomssen R (1999) Low density lipoprotein receptor as a candidate receptor for hepatitis C virus. J Med Virol 57: 223-229.
112. Monto A, Alonzo J, Watson JJ, Grunfeld C, Wright TL (2002) Steatosis in chronic hepatitis C: relative contributions of obesity, diabetes mellitus, and alcohol. Hepatology 36: 729-736.
113. Moriya K, Yotsuyanagi H, Shintani Y, Fujie H, Ishibashi K, Matsuura Y, Miyamura T, Koike K (1997) Hepatitis C virus core protein induces hepatic steatosis in transgenic mice. J Gen Virol 78(Pt 7): 1527-1531.
114. Moriya K, Fujie H, Shintani Y, Yotsuyanagi H, Tsutsumi T, Ishibashi K, Matsuura Y, Kimura S, Miyamura T, Koike K (1998) The core protein of hepatitis C virus induces hepatocellular carcinoma in transgenic mice. Nat Med 4: 1065-1067.
115. Moriya K, Nakagawa K, Santa T, Shintani Y, Fujie H, Miyoshi H, Tsutsumi T, Miyazawa T, Ishibashi K, Horie T, Imai K, Todoroki T, Kimura S, Koike K (2001) Oxidative stress in the absence of inflammation in a mouse model for hepatitis C virus-associated hepatocarcinogenesis. Cancer Res 61: 4365-4370.
116. Munday MR (2002) Regulation of mammalian acetyl-CoA carboxylase. Biochem Soc Trans 30: 1059-1064.
117. Nahmias Y, Goldwasser J, Casali M, van Poll D, Wakita T, Chung RT, Yarmush ML (2008) Apolipoprotein B-dependent hepatitis C virus secretion is inhibited by the grapefruit flavonoid naringenin. Hepatology 47: 1437-1445.
118. Neuschwander-Tetri BA, Caldwell SH (2003) Nonalcoholic steatohepatitis: summary of an AASLD Single Topic Conference. Hepatology 37: 1202-1219.
119. Nielsen SU, Bassendine MF, Martin C, Lowther D, Purcell PJ, King BJ, Neely D, Toms GL (2008) Characterization of hepatitis C RNA-containing particles from human liver by density and size. J Gen Virol 89: 2507-2517.
120. Nykjaer A, Willnow TE (2002) The low-density lipoprotein receptor gene family: a cellular Swiss army knife? Trends Cell Biol 12: 273-280.
121. Oem JK, Jackel-Cram C, Li YP, Kang HN, Zhou Y, Babiuk LA, Liu Q (2008) Hepatitis C virus non-structural protein-2 activates CXCL-8 transcription through NF-kappaB. Arch Virol 153: 293-301.
122. Oem JK, Jackel-Cram C, Li YP, Zhou Y, Zhong J, Shimano H, Babiuk LA, Liu Q (2008) Activation of sterol regulatory element-binding protein 1c and fatty acid synthase transcription by hepatitis C virus non-structural protein 2. J Gen Virol 89: 1225-1230.
123. Ohata K, Hamasaki K, Toriyama K, Matsumoto K, Saeki A, Yanagi K, Abiru S, Nakagawa Y, Shigeno M, Miyazoe S, Ichikawa T, Ishikawa H, Nakao K, Eguchi K (2003) Hepatic steatosis is a risk factor for hepatocellular carcinoma in patients with chronic hepatitis C virus infection. Cancer 97: 3036-3043.
124. Olsavsky KM, Page JL, Johnson MC, Zarbl H, Strom SC, Omiecinski CJ (2007) Gene expression profiling and differentiation assessment in primary human hepatocyte cultures, established hepatoma cell lines, and human liver tissues. Toxicol Appl Pharmacol 222: 42-56.
125. Ozes ON, Akca H, Mayo LD, Gustin JA, Maehama T, Dixon JE, Donner DB (2001) A phosphatidylinositol 3-kinase/Akt/mTOR pathway mediates and PTEN antagonizes tumor necrosis factor inhibition of insulin signaling through insulin receptor substrate-1. Proc Natl Acad Sci USA 98: 4640-4645.
126. Park CY, Jun HJ, Wakita T, Cheong JH, Hwang SB (2009) Hepatitis C virus nonstructural 4B protein modulates sterol regulatory element-binding protein signaling via the AKT pathway. J Biol Chem 284: 9237-9246.
127. Patton HM, Patel K, Behling C, Bylund D, Blatt LM, Vallee M, Heaton S, Conrad A, Pockros PJ, McHutchison JG (2004) The impact of steatosis on disease progression and early and sustained treatment response in chronic hepatitis C patients. J Hepatol 40: 484-490.
128. Pazienza V, Clement S, Pugnale P, Conzelman S, Foti M, Mangia A, Negro F (2007) The hepatitis C virus core protein of genotypes 3a and 1b downregulates insulin receptor substrate 1 through genotype-specific mechanisms. Hepatology 45: 1164-1171.
129. Pazienza V, Vinciguerra M, Andriulli A, Mangia A (2010) Hepatitis C virus core protein genotype 3a increases SOCS-7 expression through PPAR-{gamma} in Huh-7 cells. J Gen Virol 91: 1678-1686.
130. Pekow JR, Bhan AK, Zheng H, Chung RT (2007) Hepatic steatosis is associated with increased frequency of hepatocellular carcinoma in patients with hepatitis C-related cirrhosis. Cancer 109: 2490-2496.
131. Peralta C, Bartrons R, Riera L, Manzano A, Xaus C, Gelpi E, Rosello-Catafau J (2000) Hepatic preconditioning preserves energy metabolism during sustained ischemia. Am J Physiol Gastrointest Liver Physiol 279: G163-G171.
132. Perlemuter G, Sabile A, Letteron P, Vona G, Topilco A, Chretien Y, Koike K, Pessayre D, Chapman J, Barba G, Brechot C (2002) Hepatitis C virus core protein inhibits microsomal triglyceride transfer protein activity and very low density lipoprotein secretion: a model of viral-related steatosis. FASEB J 16: 185-194.
133. Persico M, Capasso M, Persico E, Svelto M, Russo R, Spano D, Croce L, La Mura V, Moschella F, Masutti F, Torella R, Tiribelli C, Iolascon A (2007) Suppressor of cytokine signaling 3 (SOCS3) expression and hepatitis C virus-related chronic hepatitis: Insulin resistance and response to antiviral therapy. Hepatology 46: 1009-1015.
134. Petit JM, Benichou M, Duvillard L, Jooste V, Bour JB, Minello A, Verges B, Brun JM, Gambert P, Hillon P (2003) Hepatitis C virus-associated hypobetalipoproteinemia is correlated with plasma viral load, steatosis, and liver fibrosis. Am J Gastroenterol 98: 1150-1154.
135. Petit JM, Minello A, Jooste V, Bour JB, Galland F, Duvillard L, Verges B, Olsson NO, Gambert P, Hillon P (2005) Decreased plasma adiponectin concentrations are closely related to steatosis in hepatitis C virus-infected patients. J Clin Endocrinol Metab 90: 2240-2243.
136. Pianko S, Patella S, Ostapowicz G, Desmond P, Sievert W (2001) Fas-mediated hepatocyte apoptosis is increased by hepatitis C virus infection and alcohol consumption, and may be associated with hepatic fibrosis: mechanisms of liver cell injury in chronic hepatitis C virus infection. J Viral Hepat 8: 406-413.
137. Pileri P, Uematsu Y, Campagnoli S, Galli G, Falugi F, Petracca R, Weiner AJ, Houghton M, Rosa D, Grandi G, Abrignani S (1998) Binding of hepatitis C virus to CD81. Science 282: 938-941.
138. Poynard T, Ratziu V, McHutchison J, Manns M, Goodman Z, Zeuzem S, Younossi Z, Albrecht J (2003) Effect of treatment with peginterferon or interferon alfa-2b and ribavirin on steatosis in patients infected with hepatitis C. Hepatology 38: 75-85.
139. Raabe M, Veniant MM, Sullivan MA, Zlot CH, Bjorkegren J, Nielsen LB, Wong JS, Hamilton RL, Young SG (1999) Analysis of the role of microsomal triglyceride transfer protein in the liver of tissue-specific knockout mice. J Clin Invest 103: 1287-1298.
140. Ramachandran CK, Gray SL, Melnykovych G (1980) Cytoplasmic 3-hydroxy-3-methylglutaryl coenzyme A synthase and the regulation of sterol synthesis in tissue culture cells. Biochim Biophys Acta 618: 439-448.
141. Ray RB, Meyer K, Ray R (1996) Suppression of apoptotic cell death by hepatitis C virus core protein. Virology 226: 176-182.
142. Reed KE, Rice CM (2000) Overview of hepatitis C virus genome structure, polyprotein processing, and protein properties. Curr Top Microbiol Immunol 242: 55-84.
143. Reyes GR (2002) The nonstructural NS5A protein of hepatitis C virus: an expanding, multifunctional role in enhancing hepatitis C virus pathogenesis. J Biomed Sci 9: 187-197.
144. Romero-Gomez M, Del Mar Viloria M, Andrade RJ, Salmeron J, Diago M, Fernandez-Rodriguez CM, Corpas R, Cruz M, Grande L, Vazquez L, Munoz-De-Rueda P, Lopez-Serrano P, Gila A, Gutierrez ML, Perez C, Ruiz-Extremera A, Suarez E, Castillo J (2005) Insulin resistance impairs sustained response rate to peginterferon plus ribavirin in chronic hepatitis C patients. Gastroenterology 128: 636-641.
145. Rouille Y, Helle F, Delgrange D, Roingeard P, Voisset C, Blanchard E, Belouzard S, McKeating J, Patel AH, Maertens G, Wakita T, Wychowski C, Dubuisson J (2006) Subcellular localization of hepatitis C virus structural proteins in a cell culture system that efficiently replicates the virus. J Virol 80: 2832-2841.
146. Rubbia-Brandt L, Quadri R, Abid K, Giostra E, Male PJ, Mentha G, Spahr L, Zarski JP, Borisch B, Hadengue A, Negro F (2000) Hepatocyte steatosis is a cytopathic effect of hepatitis C virus genotype 3. J Hepatol 33: 106-115.
147. Rubbia-Brandt L, Fabris P, Paganin S, Leandro G, Male PJ, Giostra E, Carlotto A, Bozzola L, Smedile A, Negro F (2004) Steatosis affects chronic hepatitis C progression in a genotype specific way. Gut 53: 406-412.
148. Saha AK, Avilucea PR, Ye JM, Assifi MM, Kraegen EW, Ruderman NB (2004) Pioglitazone treatment activates AMP-activated protein kinase in rat liver and adipose tissue in vivo. Biochem Biophys Res Commun 314: 580-585.
149. Santolini E, Migliaccio G, La Monica N (1994) Biosynthesis and biochemical properties of the hepatitis C virus core protein. J Virol 68: 3631-3641.
150. Sanyal AJ (2002) AGA technical review on nonalcoholic fatty liver disease. Gastroenterology 123: 1705-1725.
151. Savage DB, Choi CS, Samuel VT, Liu ZX, Zhang D, Wang A, Zhang XM, Cline GW, Yu XX, Geisler JG, Bhanot S, Monia BP, Shulman GI (2006) Reversal of diet-induced hepatic steatosis and hepatic insulin resistance by antisense oligonucleotide inhibitors of acetyl-CoA carboxylases 1 and 2. J Clin Invest 116: 817-824.
152. Scarselli E, Ansuini H, Cerino R, Roccasecca RM, Acali S, Filocamo G, Traboni C, Nicosia A, Cortese R, Vitelli A (2002) The human scavenger receptor class B type I is a novel candidate receptor for the hepatitis C virus. EMBO J 21: 5017-5025.
153. Schnitzer-Polokoff R, von Gunten C, Logel J, Torget R, Sinensky M (1982) Isolation and characterization of a mammalian cell mutant defective in 3-hydroxy-3-methylglutaryl coenzyme A synthase. J Biol Chem 257: 472-476.
154. Sekine-Osajima Y, Sakamoto N, Mishima K, Nakagawa M, Itsui Y, Tasaka M, Nishimura-Sakurai Y, Chen CH, Kanai T, Tsuchiya K, Wakita T, Enomoto N, Watanabe M (2008) Development of plaque assays for hepatitis C virus-JFH1 strain and isolation of mutants with enhanced cytopathogenicity and replication capacity. Virology 371: 71-85.
155. Sekiya M, Yahagi N, Matsuzaka T, Najima Y, Nakakuki M, Nagai R, Ishibashi S, Osuga J, Yamada N, Shimano H (2003) Polyunsaturated fatty acids ameliorate hepatic steatosis in obese mice by SREBP-1 suppression. Hepatology 38: 1529-1539.
156. Semenkovich CF (1997) Regulation of fatty acid synthase (FAS). Prog Lipid Res 36: 43-53.
157. Serfaty L, Andreani T, Giral P, Carbonell N, Chazouilleres O, Poupon R (2001) Hepatitis C virus induced hypobetalipoproteinemia: a possible mechanism for steatosis in chronic hepatitis C. J Hepatol 34: 428-434.
158. Shackel NA, McGuinness PH, Abbott CA, Gorrell MD, McCaughan GW (2002) Insights into the pathobiology of hepatitis C virus-associated cirrhosis: analysis of intrahepatic differential gene expression. Am J Pathol 160: 641-654.
159. Shavinskaya A, Boulant S, Penin F, McLauchlan J, Bartenschlager R (2007) The lipid droplet binding domain of hepatitis C virus core protein is a major determinant for efficient virus assembly. J Biol Chem 282: 37158-37169.
160. Sheehy P, Mullan B, Moreau I, Kenny-Walsh E, Shanahan F, Scallan M, Fanning LJ (2007) In vitro replication models for the hepatitis C virus. J Viral Hepat 14: 2-10.
161. Sheikh MY, Choi J, Qadri I, Friedman JE, Sanyal AJ (2008) Hepatitis C virus infection: molecular pathways to metabolic syndrome. Hepatology 47: 2127-2133.
162. Shelness GS, Sellers JA (2001) Very-low-density lipoprotein assembly and secretion. Curr Opin Lipidol 12: 151-157.
163. Shi ST, Lee KJ, Aizaki H, Hwang SB, Lai MM (2003) Hepatitis C virus RNA replication occurs on a detergent-resistant membrane that cofractionates with caveolin-2. J Virol 77: 4160-4168.
164. Shimada M, Kawahara H, Ozaki K, Fukura M, Yano H, Tsuchishima M, Tsutsumi M, Takase S (2007) Usefulness of a combined evaluation of the serum adiponectin level, HOMA-IR, and serum type IV collagen 7S level to predict the early stage of nonalcoholic steatohepatitis. Am J Gastroenterol 102: 1931-1938.
165. Shimano H, Horton JD, Hammer RE, Shimomura I, Brown MS, Goldstein JL (1996) Overproduction of cholesterol and fatty acids causes massive liver enlargement in transgenic mice expressing truncated SREBP-1a. J Clin Invest 98: 1575-1584.
166. Shimano H, Horton JD, Shimomura I, Hammer RE, Brown MS, Goldstein JL (1997) Isoform 1c of sterol regulatory element binding protein is less active than isoform 1a in livers of transgenic mice and in cultured cells. J Clin Invest 99: 846-854.
167. Shimano H (2001) Sterol regulatory element-binding proteins (SREBPs): transcriptional regulators of lipid synthetic genes. Prog Lipid Res 40: 439-452.
168. Shimomura I, Bashmakov Y, Horton JD (1999) Increased levels of nuclear SREBP-1c associated with fatty livers in two mouse models of diabetes mellitus. J Biol Chem 274: 30028-30032.
169. Shintani Y, Fujie H, Miyoshi H, Tsutsumi T, Tsukamoto K, Kimura S, Moriya K, Koike K (2004) Hepatitis C virus infection and diabetes: direct involvement of the virus in the development of insulin resistance. Gastroenterology 126: 840-848.
170. Shulman GI (2000) Cellular mechanisms of insulin resistance. J Clin Invest 106: 171-176.
171. Sidorkiewicz M, Jozwiak B, Durys B, Majda-Stanislawska E, Piekarska A, Kosciuk N, Ciechowicz J, Majewska E, Bartkowiak J (2009) Mevalonate pathway modulation is associated with hepatitis C virus RNA presence in peripheral blood mononuclear cells. Virus Res 145: 141-144.
172. Stahlberg D, Rudling M, Angelin B, Bjorkhem I, Forsell P, Nilsell K, Einarsson K (1997) Hepatic cholesterol metabolism in human obesity. Hepatology 25: 1447-1450.
173. Steer CJ (1996) Receptor-mediated endocytosis: mechanism, biologic function, and molecular properties. In: Zakim D, Boyer TD (eds) Hepatology: a text-book of liver disease volume I. WB Saunders Company, USA, pp 49-214.
174. Su AI, Pezacki JP, Wodicka L, Brideau AD, Supekova L, Thimme R, Wieland S, Bukh J, Purcell RH, Schultz PG, Chisari FV (2002) Genomic analysis of the host response to hepatitis C virus infection. Proc Natl Acad Sci USA 99: 15669-15674.
175. Suzuki T, Aizaki H, Murakami K, Shoji I, Wakita T (2007) Molecular biology of hepatitis C virus. J Gastroenterol 42: 411-423.
176. Tabor E (1989) Nonhuman primate models for non-A, non-B hepatitis. Cancer Detect Prev 14: 221-225.
177. Tachi Y, Katano Y, Honda T, Hayashi K, Ishigami M, Itoh A, Hirooka Y, Nakano I, Samejima Y, Goto H (2010) Impact of amino acid substitutions in the hepatitis C virus genotype 1b core region on liver steatosis and hepatic oxidative stress in patients with chronic hepatitis C. Liver Int 30(4): 554-559.
178. Tanaka N, Moriya K, Kiyosawa K, Koike K, Gonzalez FJ, Aoyama T (2008) PPARalpha activation is essential for HCV core protein-induced hepatic steatosis and hepatocellular carcinoma in mice. J Clin Invest 118: 683-694.
179. Tardif KD, Mori K, Kaufman RJ, Siddiqui A (2004) Hepatitis C virus suppresses the IRE1-XBP1 pathway of the unfolded protein response. J Biol Chem 279: 17158-17164.
180. Targett-Adams P, Boulant S, McLauchlan J (2008) Visualization of double-stranded RNA in cells supporting hepatitis C virus RNA replication. J Virol 82: 2182-2195.
181. Thimme R, Bukh J, Spangenberg HC, Wieland S, Pemberton J, Steiger C, Govindarajan S, Purcell RH, Chisari FV (2002) Viral and immunological determinants of hepatitis C virus clearance, persistence, and disease. Proc Natl Acad Sci USA 99: 15661-15668.
182. Tontonoz P, Hu E, Spiegelman BM (1994) Stimulation of adipogenesis in fibroblasts by PPAR gamma 2, a lipid-activated transcription factor. Cell 79: 1147-1156.
183. Tsuchida A, Yamauchi T, Ito Y, Hada Y, Maki T, Takekawa S, Kamon J, Kobayashi M, Suzuki R, Hara K, Kubota N, Terauchi Y, Froguel P, Nakae J, Kasuga M, Accili D, Tobe K, Ueki K, Nagai R, Kadowaki T (2004) Insulin/Foxo1 pathway regulates expression levels of adiponectin receptors and adiponectin sensitivity. J Biol Chem 279: 30817-30822.
184. Tsutsumi T, Suzuki T, Shimoike T, Suzuki R, Moriya K, Shintani Y, Fujie H, Matsuura Y, Koike K, Miyamura T (2002) Interaction of hepatitis C virus core protein with retinoid X receptor alpha modulates its transcriptional activity. Hepatology 35: 937-946.
185. Uysal KT, Wiesbrock SM, Marino MW, Hotamisligil GS (1997) Protection from obesity-induced insulin resistance in mice lacking TNF-alpha function. Nature 389: 610-614.
186. Vandermeeren AM, Gomez CE, Patino C, Domingo-Gil E, Guerra S, Gonzalez JM, Esteban M (2008) Subcellular forms and biochemical events triggered in human cells by HCV polyprotein expression from a viral vector. Virol J 5: 102.
187. Vidali M, Tripodi MF, Ivaldi A, Zampino R, Occhino G, Restivo L, Sutti S, Marrone A, Ruggiero G, Albano E, Adinolfi LE (2008) Interplay between oxidative stress and hepatic steatosis in the progression of chronic hepatitis C. J Hepatol 48: 399-406.
188. Wakil SJ, Stoops JK, Joshi VC (1983) Fatty acid synthesis and its regulation. Annu Rev Biochem 52: 537-579.
189. Wakita T, Taya C, Katsume A, Kato J, Yonekawa H, Kanegae Y, Saito I, Hayashi Y, Koike M, Kohara M (1998) Efficient conditional transgene expression in hepatitis C virus cDNA transgenic mice mediated by the Cre/loxP system. J Biol Chem 273: 9001-9006.
190. Wakita T, Pietschmann T, Kato T, Date T, Miyamoto M, Zhao Z, Murthy K, Habermann A, Krausslich HG, Mizokami M, Bartenschlager R, Liang TJ (2005) Production of infectious hepatitis C virus in tissue culture from a cloned viral genome. Nat Med 11: 791-796.
191. Wang AG, Lee DS, Moon HB, Kim JM, Cho KH, Choi SH, Ha HL, Han YH, Kim DG, Hwang SB, Yu DY (2009) Non-structural 5A protein of hepatitis C virus induces a range of liver pathology in transgenic mice. J Pathol 219: 253-262.
192. Wang AY, Hickman IJ, Richards AA, Whitehead JP, Prins JB, Macdonald GA (2005) High molecular weight adiponectin correlates with insulin sensitivity in patients with hepatitis C genotype 3, but not genotype 1 infection. Am J Gastroenterol 100: 2717-2723.
193. Wang T, Weinman SA (2006) Causes and consequences of mitochondrial reactive oxygen species generation in hepatitis C. J Gastroenterol Hepatol 21(Suppl 3): S34-S37.
194. Waris G, Tardif KD, Siddiqui A (2002) Endoplasmic reticulum (ER) stress: hepatitis C virus induces an ER-nucleus signal transduction pathway and activates NF-kappaB and STAT-3. Biochem Pharmacol 64: 1425-1430.
195. Waris G, Felmlee DJ, Negro F, Siddiqui A (2007) Hepatitis C virus induces proteolytic cleavage of sterol regulatory element binding proteins and stimulates their phosphorylation via oxidative stress. J Virol 81: 8122-8130.
196. Wedemeyer I, Bechmann LP, Odenthal M, Jochum C, Marquitan G, Drebber U, Gerken G, Gieseler RK, Dienes HP, Canbay A (2009) Adiponectin inhibits steatotic CD95/Fas up-regulation by hepatocytes: therapeutic implications for hepatitis C. J Hepatol 50: 140-149.
197. Westin J, Nordlinder H, Lagging M, Norkrans G, Wejstal R (2002) Steatosis accelerates fibrosis development over time in hepatitis C virus genotype 3 infected patients. J Hepatol 37: 837-842.
198. Weyer C, Funahashi T, Tanaka S, Hotta K, Matsuzawa Y, Pratley RE, Tataranni PA (2001) Hypoadiponectinemia in obesity and type 2 diabetes: close association with insulin resistance and hyperinsulinemia. J Clin Endocrinol Metab 86: 1930-1935.
199. Wiggins D, Gibbons GF (1996) Origin of hepatic very-low-density lipoprotein triacylglycerol: the contribution of cellular phospholipid. Biochem J 320(Pt 2): 673-679.
200. Winder WW, Hardie DG (1996) Inactivation of acetyl-CoA carboxylase and activation of AMP-activated protein kinase in muscle during exercise. Am J Physiol 270: E299-E304.
201. Wolf AM, Wolf D, Rumpold H, Enrich B, Tilg H (2004) Adiponectin induces the anti-inflammatory cytokines IL-10 and IL-1RA in human leukocytes. Biochem Biophys Res Commun 323: 630-635.
202. Xu A, Wang Y, Keshaw H, Xu LY, Lam KS, Cooper GJ (2003) The fat-derived hormone adiponectin alleviates alcoholic and nonalcoholic fatty liver diseases in mice. J Clin Invest 112: 91-100.
203. Xu X, Chen H, Cao X, Ben K (2007) Efficient infection of tree shrew (Tupaia belangeri) with hepatitis C virus grown in cell culture or from patient plasma. J Gen Virol 88: 2504-2512.
204. Yamaguchi A, Tazuma S, Nishioka T, Ohishi W, Hyogo H, Nomura S, Chayama K (2005) Hepatitis C virus core protein modulates fatty acid metabolism and thereby causes lipid accumulation in the liver. Dig Dis Sci 50: 1361-1371.
205. Yamauchi T, Kamon J, Minokoshi Y, Ito Y, Waki H, Uchida S, Yamashita S, Noda M, Kita S, Ueki K, Eto K, Akanuma Y, Froguel P, Foufelle F, Ferre P, Carling D, Kimura S, Nagai R, Kahn BB, Kadowaki T (2002) Adiponectin stimulates glucose utilization and fatty-acid oxidation by activating AMP-activated protein kinase. Nat Med 8: 1288-1295.
206. Yamauchi T, Kamon J, Ito Y, Tsuchida A, Yokomizo T, Kita S, Sugiyama T, Miyagishi M, Hara K, Tsunoda M, Murakami K, Ohteki T, Uchida S, Takekawa S, Waki H, Tsuno NH, Shibata Y, Terauchi Y, Froguel P, Tobe K, Koyasu S, Taira K, Kitamura T, Shimizu T, Nagai R, Kadowaki T (2003) Cloning of adiponectin receptors that mediate antidiabetic metabolic effects. Nature 423: 762-769.
207. Yamauchi T, Nio Y, Maki T, Kobayashi M, Takazawa T, Iwabu M, Okada-Iwabu M, Kawamoto S, Kubota N, Kubota T, Ito Y, Kamon J, Tsuchida A, Kumagai K, Kozono H, Hada Y, Ogata H, Tokuyama K, Tsunoda M, Ide T, Murakami K, Awazawa M, Takamoto I, Froguel P, Hara K, Tobe K, Nagai R, Ueki K, Kadowaki T (2007) Targeted disruption of AdipoR1 and AdipoR2 causes abrogation of adiponectin binding and metabolic actions. Nat Med 13: 332-339.
208. Yang W, Huang M (2009) Studying HCV RNA synthesis in vitro with replication complexes. Methods Mol Biol 510: 177-184.
209. Ye J, Wang C, Sumpter R Jr, Brown MS, Goldstein JL, Gale M Jr (2003) Disruption of hepatitis C virus RNA replication through inhibition of host protein geranylgeranylation. Proc Natl Acad Sci USA 100: 15865-15870.
210. Yokota T, Oritani K, Takahashi I, Ishikawa J, Matsuyama A, Ouchi N, Kihara S, Funahashi T, Tenner AJ, Tomiyama Y, Matsuzawa Y (2000) Adiponectin, a new member of the family of soluble defense collagens, negatively regulates the growth of myelomonocytic progenitors and the functions of macrophages. Blood 96: 1723-1732.
211. You M, Matsumoto M, Pacold CM, Cho WK, Crabb DW (2004) The role of AMP-activated protein kinase in the action of ethanol in the liver. Gastroenterology 127: 1798-1808.
212. Zein CO, Levy C, Basu A, Zein NN (2005) Chronic hepatitis C and type II diabetes mellitus: a prospective cross-sectional study. Am J Gastroenterol 100: 48-55.
213. Zekri AR, Bahnassy AA, El-Din HM, Salama HM (2009) Consensus siRNA for inhibition of HCV genotype-4 replication. Virol J 6: 13.
214. Zhong J, Gastaminza P, Cheng G, Kapadia S, Kato T, Burton DR, Wieland SF, Uprichard SL, Wakita T, Chisari FV (2005) Robust hepatitis C virus infection in vitro. Proc Natl Acad Sci USA 102: 9294-9299.
215. Zhou G, Myers R, Li Y, Chen Y, Shen X, Fenyk-Melody J, Wu M, Ventre J, Doebber T, Fujii N, Musi N, Hirshman MF, Goodyear LJ, Moller DE (2001) Role of AMP-activated protein kinase in mechanism of metformin action. J Clin Invest 108: 1167-1174.
216. Zhu N, Khoshnan A, Schneider R, Matsumoto M, Dennert G, Ware C, Lai MM (1998) Hepatitis C virus core protein binds to the cytoplasmic domain of tumor necrosis factor (TNF) receptor 1 and enhances TNF-induced apoptosis. J Virol 72: 3691-3697.
217. Zhu Q, Oei Y, Mendel DB, Garrett EN, Patawaran MB, Hollenbach PW, Aukerman SL, Weiner AJ (2006) Novel robust hepatitis C virus mouse efficacy model. Antimicrob Agents Chemother 50: 3260-3268.