2013, Number 3
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Ann Hepatol 2013; 12 (3)
Differential expression of transforming growth factor-β and HBx enhances hepatitis B virus replication and augments host immune cytokines and chemokines
Almajhdi FN, Al-Qudari AY, Hussain Z
Language: English
References: 42
Page: 408-415
PDF size: 207.25 Kb.
ABSTRACT
Background/Aims. This study investigated how HBV replication and host immune response are effected by
reduced expression of TGF-β1 and HBx.
Material and methods. Short interfering RNA (siRNA) knockdown
technology has been used to examine the role of TGF-β1 in hepatitis B virus replication. The siTGF-β1 has
been transfected along with 1.3mer HBV x-null to investigate the knockdown effect of TGF-β1 on HBV replication
and host immune factors.
Results. In this study, we found that diminished expression of TGF-β1
and increased expression of HBx enhances HBV replication several folds. The differential expression of
TGF-β1 and HBx also stimulated transcriptional viral replicative intermediate (pgRNA) and secretion of core
and ‘e’ antigen at translational level. Consequently, several cytokines such as IL-2, IL-8 and chemokine monocyte-
chemoattractant protein (MCP-1) were increased significantly in response to stimulation of HBV replication.
In contrast, TNF-α and RANTES mRNA expression increased insignificantly in response to
enhanced HBV replication.
Conclusions. We concluded that reduced expression of TGF-β1 together with
HBx expression stimulate HBV replication and immune response, although the underlying mechanism of stimulation
most likely differs.
REFERENCES
Kao JH, Chen DS. Global control of hepatitis B virus infection. Lancet Infect Dis 2002; 2: 395-403.
Wright TL, Lau JY. Clinical aspects of hepatitis B virus infection. Lancet 1993: 342: 1340-4.
Ganem D, Prince AM. Hepatitis B virus infection-natural history and clinical consequences. N Engl J Med 2004; 350: 1118-29.
Sherlock S. Viruses and hepatocellular carcinoma. Gut 1994; 35: 828-32.
Malik R, Selden C, Hodgson H. The role of non-parenchymal cells in liver growth. Semin Cell Dev Biol 2002; 13: 425-31.
Seeger C, Mason WS. Hepatitis B virus biology. Microbiol Mol Biol Rev 2000; 64: 51-68.
Ramadori G, Armbrust T. Cytokines in the liver. Eur J Gastroenterol Hepatol 2001: 13: 777-84.
Andrisani OM, Barnabas S. The transcriptional function of the hepatitis B virus X protein and its role in hepatocarcinogenesis. Int J Oncol 1999;15: 373-9.
McClary H, Koch R, Chisari FV, Guidotti LG. Relative sensitivity of hepatitis B virus and other hepatotropic viruses to the antiviral effects of cytokines. J Virol 2000; 74: 2255-64.
Guidotti LG, Morris A, Mendez H, Koch R, Silverman RH, Williams BR, et al. Interferon-regulated pathways that control hepatitis B virus replication in transgenic mice. J Virol 2002; 76: 2617-21.
Pasquetto V, Wieland SF, Uprichard SL, Tripodi M, Chisari FV. Cytokine-sensitive replication of hepatitis B virus in immortalized mouse hepatocyte cultures. J Virol 2002; 76: 5646-53.
Guidotti LG, Rochford R, Chung L, Shapiro M, Purcell R, Chisari FV. Viral clearance without destruction of infected cells during acute HBV infection. Science 1999; 284: 825-9.
Chisari FV, Ferrari C. Hepatitis B virus immunopathogenesis. Annu Rev Immunol 1995; 13: 29-60.
Thimme R, Wieland S, Steiger C, Ghrayeb J, Reimann KA, Purcell RH, et al. CD8(+) T cells mediate viral clearance and disease pathogenesis during acute hepatitis B virus infection. J Virol 2003; 77: 68-76.
Isogawa M, Robek MD, Furuichi Y, Chisari FV. Toll-like receptor signaling inhibits hepatitis B virus replication in vivo. J Virol 2005; 79: 7269-72.
Kimura K, Kakimi K, Wieland S, Guidotti LG, Chisari FV. Interleukin- 18 inhibits hepatitis B virus replication in the livers of transgenic mice. J Virol 2002; 76: 10702-07.
Kimura K, Kakimi K, Wieland S, Guidotti LG, Chisari FV. Activated intrahepatic antigen-presenting cells inhibit hepatitis B virus replication in the liver of transgenic mice. J Immunol 2002; 169: 5188-95.
Kakimi K, Lane TE, Chisari FV, Guidotti LG. Cutting edge: Inhibition of hepatitis B virus replication by activated NK T cells does not require inflammatory cell recruitment to the liver. J Immunol 2001; 167: 6701-05.
Kakimi K, Guidotti LG, Koezuka Y, Chisari FV. Natural killer T cell activation inhibits hepatitis B virus replication in vivo. J Exp Med 2000; 192: 921-30.
Koyama AH, Irie H, Fukomori T, et al. Role of virus-induced apoptosis in a host defence mechanism against virus infection. J Med Invest 1998; 45: 37-45.
Samuel CE. Antiviral actions of interferons. Clin Microbiol Rev 2001; 14: 778-809.
Biron CA, Nguyen KB, Pien GC, Cousens LP, Salazar-Mather TP. Natural killer cells in antiviral defense: function and regulation by innate cytokines. Annu Rev Immunol 1999; 17: 189-220.
Guidotti LG, Chisari FV. Noncytolytic control of viral infections by the innate and adaptive immune response. Annu Rev Immunol 2001; 19: 65-91.
Iannacone M, Sitia G, Guidotti LG. Pathogenetic and antiviral immune responses against hepatitis B virus. Future Virol 2006; 1: 189-96.
Sales VL, Engelmayr GC, Mettler BA, Johnson JA, Sacks MS, Mayer JE. Transforming growth factor-beta1 modulates extracellular matrix production, proliferation, and apoptosis of endothelial progenitor cells in tissue-engineering scaffolds. Circulation 2006; 114: I193-I199.
Kanzler S, Baumann M, Schirmacher P, Dries V, Bayer E, Gerken G, Dienes HP, et al. Prediction of progressive liver fibrosis in hepatitis C infection by serum and tissue levels of transforming growth factor-beta. J Viral Hepat 2001; 8: 430-7.
Migita K, Miyazoe S, Maeda Y, Daikoku M, Abiru S, Ueki T, Yano K, et al. Cytokine gene polymorphisms in Japanese patients with hepatitis B virus infection-association between TGF-beta1 polymorphisms and hepatocellular carcinoma. J Hepatol 2005; 42: 505-10.
Lewis MP, Lygoe KA, Nystrom ML, Anderson WP, Speight PM, Marshall JF, Thomas GJ. Tumour-derived TGF-beta1 modulates myofibroblast differentiation and promotes HGF/SF-dependent invasion of squamous carcinoma cells. Br J Cancer 2004; 90: 822-32.
Chou YC, Chen ML, Hu CP, Chen YL, Chong CL, Tsai YL, Liu TL, et al. Transforming growth factor-beta1 suppresses hepatitis B virus replication primarily through transcriptional inhibition of pregenomic RNA. Hepatology 2007; 46: 672-81.
Hong MH, Chou YC, Wu YC, Tsai KN, Hu CP, Jeng KS, Chen ML, et al. Transforming growth factor-b1 suppresses hepatitis B virus replication by the reduction of hepatocyte nuclear factor-4a expression. PLoS One 2012; 7: e30360.
Tang H, Oishi N, Kaneko S, Murakami S. Molecular functions and biological roles of hepatitis B virus x protein. Cancer Sci 2006; 97: 977-83.
Pang R, Tse E, Poon RT. Molecular pathways in hepatocellular carcinoma. Cancer Lett 2006; 240: 157-69.
Hussain Z, Jung HS, Ryu DK, Ryu WS. Genetic dissection of naturally occurring basal core promoter mutations of hepatitis B virus reveals a silent phenotype in the overlapping X gene. J Gen Virol 2009; 90: 2272-81.
Cha MY, Ryu DK, Jung HS, Chang HE, Ryu WS. Stimulation of hepatitis B virus genome replication by HBx is linked to both nuclear and cytoplasmic HBx expression. J Gen Virol 2009; 90: 978-86.
Pugh J C, Yaginuma K, Koike K, Summers J. Duck hepatitis B virus (DHBV) particles produced by transient expression of DHBV DNA in a human hepatoma cell line are infectious in vitro. J Virol 1988; 62: 3513-16.
Shin MK, Lee J, Ryu WS. A novel cis-acting element facilitates minus-strand DNA synthesis during reverse transcription of the hepatitis B viruses genome. J Virol 2004; 78: 6252-62.
Chomczynski P, Sacchi N. Single-step method of RNA isolation by acid guanidinium thiocyanate-phenol-chloroform extraction. Anal Biochem 1987; 162: 156-59.
Jeong JK, Yoon GS, Ryu WS. Evidence that the 5'-end cap structure is essential for encapsidation of hepatitis B virus pregenomic RNA. J Virol 2000; 74: 5502-08.
Murawaki Y, Nishimura Y, Ikuta Y, Idobe Y, Kitamura Y, Kawasaki H. Plasma transforming growth factor-beta 1 concentrations in patients with chronic viral hepatitis. J Gastroenterol Hepatol 1998; 13: 680-4.
Akpolat N, Yahsi S, Godekmerdan A, Demirbag K, Yalniz M. Relationship between serum cytokine levels and histopathological changes of liver in patients with hepatitis B. World J Gastroenterol 2005; 11: 3260-63.
Shirai Y, Kawata S, Tamura S, Ito N, Tsushima H, Takaishi K, et al. Plasma transforming growth factor-beta 1 in patients with hepatocellular carcinoma. Comparison with chronic liver diseases. Cancer 1994; 73: 2275-9.
Koziel MJ. Cytokines in viral hepatitis. Semin Liver Dis 1999; 19: 157-69.