NS3-4A and NS4A proteins of hepatitis C virus regulate the apoptotic proteins expression in Huh-7 cells

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Research Paper 01/11/2015
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NS3-4A and NS4A proteins of hepatitis C virus regulate the apoptotic proteins expression in Huh-7 cells

Farakh Javed, Sobia Manzoor, Aamer Ali Khattak, Naureen Aurangzeb, Sadiq Noor Khan, Darima Habib, Afshan Saleem
Int. J. Biosci. 7(5), 9-15, November 2015.
Copyright Statement: Copyright 2015; The Author(s).
License: CC BY-NC 4.0

Abstract

Almost 2 % of the world population is infected with Hepatitis C virus (HCV). Prolonged HCV infection often results in the development of chronic hepatitis, liver cirrhosis and hepatocellular carcinoma (HCC) that is severe health problem worldwide. Aim of the current study was to check the role of HCV non-structural NS3-4A and NS4A proteins in the regulation of mitochondrial death pathway. Recombinant vectors containing HCV non-structural NS3-4A and NS4A proteins were transfected in Huh-7 cells and their transfection efficacy were observed. Further confocal microscopy was used to observe the accumulation of HCV the non-structural proteins NS3-4A and NS4A to mitochondria. Western blot analysis shown down regulated expression of Bcl-2protein which is anti-apoptotic in nature in the HCV non-structural NS3-4A and NS4A expressing Huh-7 cells. Bad protein which is basically pro-apoptotic in nature shown up regulated expression in NS3-4A and NS4A expressing Huh-7 cells. Furthermore HCV non-structural NS3-4A and NS4A proteins expressing Huh-7 cells have shown the activation of executioner procaspase-3 which is the final pro-apoptotic mediator that cleavage the numerous structural and regulatory cellular proteins. In conclusion HCV non-structural NS3-4A and NS4A proteins have shown regulation of apoptotic proteins that are clear indicator of the induction of mitochondrial death pathway.

Ali SA, Donahue RM, Qureshi H, Vermund SH. 2009. Hepatitis B and hepatitis C in Pakistan: prevalence and risk factors. International Journal of Infectious Diseases 13, 9-19. http://dx.doi.org/10.1016/j.ijid.2008.06.019

Ashkenazi A, Dixit VM. 1998. Death  receptors: signaling and modulation. Science 281, 1305-1308. http://dx.doi.org/10.1126/science.281.5381.1305

Bieche I, Asselah T, Laurendeau I, Vidaud D, Degot C. 2005. Molecular profiling of early stage liver fibrosis in patients with chronic hepatitis C virus infection. Virology 332, 130-144. http://dx.doi.org/10.1016/j.virol.2004.11.009

Choo QL, Kuo G, Weiner AJ, Overby LR, Bradley DW, Houghton M. 1989.Isolation of a cDNA clone derived from a blood-borne non-A, non-B viral hepatitis genome. Science 244, 359-362. http://dx.doi.org/10.1126/science.2523562

Fischer R, Baumert T, Blum HE. 2007. Hepatitis C virus infection and apoptosis. World Journal Gastroenterology 13, 4865-4872.

Galle J, Herzog C, Schollmeyer P, Wanner C. 1994. Oxygen-derived radicals stimulate renin release of isolated juxtaglomerular cells. FEBS Letter 351, 314-316. http://dx.doi.org/10.1016/0014-5793(94)00853-1

Gewies A, Rokhlin OW, Cohen MB. 2000. Cytochrome c is involved in Fas-mediated apoptosis of prostatic carcinoma cell lines. Cancer Res. 60, 2163-2168.

Ghaziani T, Shan Y, Lambrecht RW, Donohue SE, Pietschmann T, Bartenschlager R, Bonkovsky HL. 2006. HCV proteins increase expression of heme oxygenase-1 (HO-1) and decrease expression of Bach1 in human hepatoma cells. Journal of Hepatology 45, 5-12. http://dx.doi.org/10.1016/j.jhep.2005.12.020

Gottwein JM, Scheel TK, Callendret B, Li YP, Eccleston HB, Engle RE, Govindarajan S, Satterfield W, Purcell RH, Walker CM, Bukh J. 2010. Novel infectious cDNA clones of hepatitis C virus genotype 3a (strain S52) and 4a (strain ED43): genetic analyses and in vivo pathogenesis studies. Journal of Virology 84, 5277-5293. http://dx.doi.org/10.1128/jvi.02667-09

Green DR. 2000. Apoptotic pathways. Cell, 102, 1-4. http://dx.doi.org/10.1016/s0092-8674(00)00003-9

Kang X, ChenX, He Y, GuoD, GuoL, ZhongJ, ShuHB. 2013. DDB1 is a cellular substrate of NS3/4A protease and required for hepatitis C virus replication.Virology 435, 385-94. http://dx.doi.org/10.1016/j.virol.2012.10.025

Kuang WF, Lin YC, Jean F, Huang YW, Tai CL, Chen DS, Chen PJ, Hwang LH. 2004. Hepatitis C virus NS3 RNA helicase activity is modulated by the two domains of NS3 and NS4A. Biochemical and Biophysical Research Communications 317, 211-217. http://dx.doi.org/10.1016/j.bbrc.2004.03.032

Kumar S. 2007. Caspase function in programmed cell death. Cell Death and Differentiation 14, 32-43. http://dx.doi.org/10.1038/sj.cdd.4402060

Lavanchy D. 2009. The global burden of hepatitis C. Liver International 29, 74-81. http://dx.doi.org/10.1111/j.1478-3231.2008.01934.x

Liu C, Gaca M, Swenson ES, Vellucci VF, Reiss M,  Wells  RG.  2003.  Smad2  and  Sn-mad3  are differentially activated by transforming growth factor beta in quiscent and avctivated hepatic stellate cells in TGF- beta independent. Journal of Biological Chemistry 278, 1172-1178. http://dx.doi.org/10.1074/jbc.m207728200

Owen RA, Molon-Noblot S, Hubert MF, Kindt MV, Keenan KP, Eydelloth RS, 1994. The morphology of juxtaglomerular cell hyperplasia and hypertrophy in normotensive rats and monkeys given an  angiotensin  II  receptor  antagonist.  Toxicologic Pathology 22, 606-19. http://dx.doi.org/10.1177/019262339402200605

Pang PS, Jankowsky E, Planet PJ, Pyle AM.2002. The hepatitis C viral NS3 protein is a processive DNA helicase with cofactor enhanced RNA unwinding. The EMBO Journal 21, 1168-1176. http://dx.doi.org/10.1093/emboj/21.5.1168

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. http://dx.doi.org/10.1002/cncr.22701

Qadri I, IwahashiM, Kullak-Ublick GA, Simon FR. 2006. Hepatocyte Nuclear Factor (HNF) 1 and HNF4 Mediate Hepatic Multidrug Resistance Protein 2 Up-Regulation during Hepatitis C Virus Gene Expression. Molecular Pharmacology 70, 627-636. http://dx.doi.org/10.1124/mol.106.023499

Reed KE, Rice CM. 2000. Overview of hepatitis C virus genome structure, polyprotein processing, and protein properties. Current Topics in Microbiology and Immunology 242, 55-84. http://dx.doi.org/10.1007/978-3-642-59605-6_4

Ruggieri A, Harada T, Matsuura Y, Miyamura T. 1997. Sensitization to Fas-mediated apoptosis by hepatitis C virus core protein. Virology 229, 68-76. http://dx.doi.org/10.1006/viro.1996.8420

Saito T, Miyamura A, Ohbayashi H, Harada T, Katayama S, Kikuchi Y, Watanabe S, Koi M, Onji Y, Ohta. 1990. Hepatitis C virus infection is associated  with  the  development  of  hepatocellular carcinoma. Proceedings of the National Academy of Sciences 87, 6547-6549. http://dx.doi.org/10.1073/pnas.87.17.6547

Shen Y, Shenk TE. 1995. Viruses and apoptosis. Current Opinion in Genetics & Development 5, 105-111. http://dx.doi.org/10.1016/s0959-437x(95)90061-6

White E. 1996. Life, death, and the pursuit of apoptosis.Genes & Development 10, 1-15. http://dx.doi.org/10.1101/gad.10.1.1

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