Health> Vol.5 No.9, September 2013

Cytokine gene expression in human hepatocytes infected with dengue virus serotype 3 (strain-16562)

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ABSTRACT

Liver is a site of viral replication and liver dysfunction is a characteristic of severe dengue infection. To understand these mechanisms, we analyzed the response of a hepatic cell linage, HepG2 to infection with dengue 3 virus (strain 16562). Steady state levels of mRNA accumulation were assessed for 14 genes involved in modulation of the host immune responses, at 6, 24 and 48 hpi, by quantitative reverse transcription real-time PCR (qRT-PCR). Fourteen genes showed altered expression upon infection with D3V including; cytokines/chemokines (IL-1β, IL-6, IL-8, RANTES, MCP-2, IL-2Rα and TGF-βIIIR), type I interferon (IFN-α and IFN-β), and pattern-recognition receptors (TLR3, TLR8, RIG-1, MDA5 and MyD88). Although these genes are associated with mechanism of innate immune response and anti-viral activity, their altered expression does not inhibit D3V (strain 16562) growth kinetics and virus yield in HepG2 cells. Gene expression in liver may explain pathological changes associated with dengue virus infection.

Cite this paper

Yoksan, S. , Rabablert, J. , Chaiyo, K. , Rajchakam, S. , Tiewcharoen, S. , Rabablert, N. , Kerdkriangkrai, S. , Samngamnim, N. , Phurttikul, W. and Luangboribun, T. (2013) Cytokine gene expression in human hepatocytes infected with dengue virus serotype 3 (strain-16562). Health, 5, 1516-1525. doi: 10.4236/health.2013.59206.

References

[1] Conceicao, T.M., El-Bacha, T., Villas-Boas, C.S., Coello, G., Ramírez, J., Montero-Lomeli M. and Da Poian, A.T. (2010) Gene expression analysis during dengue virus infection in HepG2 cells reveals virus control of innate immune response. Journal of Infection, 60, 65-75. doi:10.1016/j.jinf.2009.10.003
[2] Rabablert, J. and Yoksan, S. (2009) Attenuated D2 16681-PDK53 vaccine: Defining humoral and cell-mediated immunity. Current Pharmaceutical Design, 15, 1203-1211. doi:10.2174/138161209787846865
[3] Hugo, L.E., Monkman, J., Dave, K.A., Wockner, L.F., Birrell, G.W., Norris, E.L., Kienzle, V.J., Sikulu, M.T., Ryan, P.A., Gorman, J.J. and Kay, B.H. (2013) Proteomic biomarkers for ageing the mosquito Aedes aegypti to determine risk of pathogen transmission. PLoS One, 8, e58656. doi:10.1371/journal.pone.0058656
[4] Vega-Rua, A., Zouache, K., Caro, V., Diancourt, L., Delaunay, P., Grandadam, M. and Failloux, A.B. (2013) High efficiency of temperate Aedes albopictus to transmit chikungunya and dengue viruses in the Southeast of France. PLoS One, 8, e59716. doi:10.1371/journal.pone.0059716
[5] Martina, B.E., Koraka, P. and Osterhaus, A.D. (2009) Dengue virus pathogenesis: An integrated view. Clinical Microbiology Review, 22, 564-581. doi:10.1128/CMR.00035-09
[6] Nagila, A., Permpongpaiboon, T., Tantrarongroj, S., Porapakkham, P., Chinwattana, K., Deakin, S. and Porntadavity, S. (2009) Effect of atorvastatin on paraoxonase1 (PON1) and oxidative status. Pharmacological Report, 61, 892-898. http://www.if-pan.krakow.pl/pjp/pdf/2009/5_892.pdf
[7] Huerre, M.R., Lan, N.T., Marianneau, P., Hue, N.B., Khun, H., Hung, N.T., Khen, N.T., Drouet, M.T., Huong, V.T., Ha, D.Q., Buisson, Y. and Deubel, V. (2001) Liver histopathology and biological correlates in five cases of fatal dengue fever in Vietnamese children. Virchows Archives, 438, 107-115. doi:10.1007/s004280000329
[8] Mohan, B., Patwari, A.K. and Anand, V.K. (2000) Hepatic dysfunction in childhood dengue infection. Journal of Tropical Pediatrics, 46, 40-43. doi:10.1093/tropej/46.1.40
[9] Subramanian, V., Shenoy, S. and Joseph, A.J. (2005) Dengue hemorrhagic fever and fulminant hepatic failure. Digestive Diseases and Sciences, 50, 1146-1147. doi:10.1007/s10620-005-2722-6
[10] Ling, L.M., Wilder-Smith, A. and Leo, Y.S. (2007) Fulminant hepatitis in dengue haemorrhagic fever. Journal of Clinical Virology, 38, 265-268. doi:10.1016/j.jcv.2006.12.011
[11] Bhamarapravati, N. (1989) Hemostatic defects in dengue hemorrhagic fever. Reviews of Infectious Diseases, 11, S826-S829. http://www.jstor.org/stable/4454972
[12] Nasirudeen, A.M., Wong, H.H., Thien, P., Xu, S., Lam, K.P. and Liu, D.X. (2011) RIG-I, MDA5 and TLR3 synergistically play an important role in restriction of dengue virus infection. PLOS Neglected Tropical Diseases, 4, 5. doi:10.1371/journal.pntd.0000926
[13] Nagila, A., Netsawang, J., Srisawat, C., Noisakran, S., Morchang, A., Yasamut, U., Puttikhunt, C., Kasinrerk, W., Malasit, P., Yenchitsomanus, P.T. and Limjindaporn, T. (2011) Role of CD137 signaling in dengue virus-mediated apoptosis. Biochemical and Biophysical Research Communications, 410, 428-433. doi:10.1016/j.bbrc.2011.05.151
[14] Seth, R.B., Sun, L. and Chen, Z.J. (2006) Antiviral innate immunity pathways. Cell Research, 16, 141-147. doi:10.1038/sj.cr.7310019
[15] Meylan, E. and Tschopp, J. (2006) Toll-like receptors and RNA helicases: Two parallel ways to trigger antiviral responses. Molecular Cell, 22, 561-569. doi:10.1016/j.molcel.2006.05.012
[16] Barton, G.M. (2007) Viral recognition by toll-like recaptors. Seminars in Immunology, 19, 33-40. doi:10.1016/j.smim.2007.01.003
[17] Wang, J.P., Liu, P., Latz, E., Golenbock, D.T., Finberg, R.W. and Libraty, D.H. (2006) Flavivirus activation of plasmacytoid dendritic cells delineates key elements of TLR7 signaling beyond endosomal recognition. The Journal of Immunology, 177, 7114-7121. http://www.jimmunol.org/content/177/10/7114.long
[18] Sun, P., Fernandez, S., Marovich, M.A., Palmer, D.R., Celluzzi, C.M., Boonnak, K., Liang, Z., Subramanian, H., Porter, K.R., Sun, W. and Burgess, T.H. (2009) Functional characterization of ex vivo blood myeloid and plasmacytoid dendritic cells after infection with dengue virus. Virology, 383, 207-215. doi:10.1016/j.virol.2008.10.022
[19] Tsai, Y.T., Chang, S.Y., Lee, C.N. and Kao, C.L. (2009) Human TLR3 recognizes dengue virus and modulates viral replication in vitro. Cellular Microbiology, 11, 604-615. doi:10.1111/j.1462-5822.2008.01277.x
[20] Loo, Y.M., Fornek, J., Crochet, N., Bajwa, G., Perwitasari, O., Martinez-Sobrido, L., Akira, S., Gill, M.A., GarcíaSastre, A., Katze, M.G. and Gale Jr., M. (2008) Distinct RIG-I and MDA5 signaling by RNA viruses in innate immunity. Journal of Virology, 82, 335-345. doi:10.1128/JVI.01080-07
[21] Chang, T.H., Liao, C.L. and Lin, Y.L. (2006) Flavivirus induces interferon-beta gene expression through a pathway involving RIG-I-dependent IRF-3 and PI3K-dependent NF-kappaB activation. Microbes and Infection, 8, 157-171. doi:10.1016/j.micinf.2005.06.014
[22] Johnson, B.W., Russell, B.J., Lanciotti, R.S. (2005) Serotype-specific detection of dengue viruses in a fourplex real-time reverse transcriptase PCR assay. Journal of Clinical Microbiology, 43, 4977-4983. doi:10.1128/JCM.43.10.4977-4983.2005
[23] Limonta, D., Capó, V., Torres, G., Pérez, A.B. and Guzmán, M.G. (2007) Apoptosis in tissues from fatal dengue shock syndrome. Journal of Clinical Virology, 40, 50-54. doi:10.1016/j.jcv.2007.04.024
[24] Paes, M.V., Pinhao, A.T., Barreto, D.F., Costa, S.M., Oliveira, M.P., Nogueira, A.C., Takiya, C.M., Farias-Filho, J.C., Schatzmayr, H.G., Alves, A.M. and Barth, O.M. (2005) Liver injury and viremia in mice infected with dengue-2 virus. Virology, 338, 236-246. doi:10.1016/j.virol.2005.04.042
[25] Seneviratne, S.L., Malavige, G.N. and de Silva, H.J. (2006) Pathogenesis of liver involvement during dengue viral infections. Transactions of the Royal Society of Tropical Medicine and Hygiene, 100, 608-614. doi:10.1016/j.trstmh.2005.10.007
[26] Pattanakitsakul, S.N., Rungrojcharoenkit, K., Kanlaya, R., Sinchaikul, S., Noisakran, S., Chen, S.T., Malasit, P. and Thongboonkerd, V. (2007) Proteomic analysis of host responses in HepG2 cells during dengue virus infection. Journal of Proteome Research, 6, 4592-4600. doi:10.1021/pr070366b
[27] Silva, B.M., Sousa, L.P., Gomes-Ruiz, A.C., Leite, F.G., Teixeira, M.M., da Fonseca, F.G., Pimenta, P.F., Ferreira, P.C., Kroon, E.G. and Bonjardim, C.A. (2011) The dengue virus nonstructural protein 1 (NS1) increases NF-κB transcriptional activity in HepG2 cells. Archives of Virology, 156, 1275-1279. doi:10.1007/s00705-011-0969-0
[28] Assuncao-Miranda, I., Amaral, F.A., Bozza, F.A., Fagundes, C.T., Sousa, L.P., Souza, D.G., Pacheco, P., BarbosaLima, G., Gomes, R.N., Bozza, P.T., Da Poian, A.T., Teixeira, M.M. and Bozza, M.T. (2010) Contribution of macrophage migration inhibitory factor to the pathogenesis of dengue virus infection. The FASEB Journal, 24, 218-228. doi:10.1096/fj.09-139469
[29] Warke, R.V., Xhaja, K., Martin, K.J., Fournier, M.F., Shaw, S.K., Brizuela, N., de Bosch, N., Lapointe, D., Ennis, F.A., Rothman, A.L. and Bosch, I. (2003) Dengue virus induces novel changes in gene expression of human umbilical vein endothelial cells. Journal of Virology, 77, 11822-11832. doi:10.1128/JVI.77.21.11822-11832.2003
[30] Rabablert, J., Wasi, C., Kinney, R., Kasisith, J., Pitidhammabhorn, D. and Ubol, S. (2007) Attenuating characteristics of DEN-2 PDK53 in flavivirus-naive peripheral blood mononuclear cells. Vaccine, 25, 3896-3905.
[31] Leong, A.S., Wong, K.T., Leong, T.Y., Tan, P.H. and Wannakrairot, P. (2007) The pathology of dengue hemorrhagic fever. Seminars in Diagnostic Pathology, 24, 227-236. doi:10.1053/j.semdp.2007.07.002
[32] Restrepo, B.N., Isaza, D.M., Salazar, C.L., Ramírez, R., Ospina, M. and Alvarez, L.G. (2008) Serum levels of interleukin-6, tumor necrosis factor-alpha and interferongamma in infants with and without dengue. Revista da Sociedade Brasileira de Medicina Tropical, 41, 6-10. doi:10.1590/S0037-86822008000100002
[33] Lei, H.Y., Yeh, T.M., Liu, H.S., Lin, Y.S., Chen, S.H. and Liu, C.C. (2001) Immunopathogenesis of dengue virus infection. Journal of Biomedical Science, 8, 377-388. doi:10.1007/BF02255946
[34] Gabay, C. (2006) Interleukin-6 and chronic inflammation. Arthritis Research & Therapy, 8, S2-S3. doi:10.1186/ar1917
[35] Lipsky, P.E. (2006) Interleukin-6 and rheumatic diseases. Arthritis Research & Therapy, 8, S2-S4. doi:10.1186/ar1918
[36] Bray, M. (2005) Pathogenesis of viral hemorrhagic fever. Current Opinion in Immunology, 17, 399-403. doi:10.1016/j.coi.2005.05.001
[37] Dejica, D. (2001) Serum soluble IL-2 receptor as a marker of lymphocyte activation in some autoimmune diseases. Effect of immunosuppressive therapy. Romanian Archives of Microbiology and Immunology, 60, 183-201. http://www.ncbi.nlm.nih.gov/pubmed/12165973
[38] Blobe, G.C., Liu, X., Fang, S.J., How, T. and Lodish, H.F. (2001) A novel mechanism for regulating transforming growth factor beta (TGF-beta) signaling. Functional modulation of type III TGF-beta receptor expression through interaction with the PDZ domain protein, GIPC. The Journal of Biological Chemistry, 276, 39608-39617. doi:10.1074/jbc.M106831200
[39] Kinter, A.L., Poli, G., Fox, L., Hardy, E. and Fauci, A.S. (1995) HIV replication in IL-2-stimulated peripheral blood mononuclear cells is driven in an autocrine/paracrine manner by endogenous cytokines. The Journal of Immunology, 154, 2448-2459. http://www.jimmunol.org/content/154/5/2448.abstract
[40] Talavera, D., Castillo, A.M., Dominguez, M.C., Gutierrez, A.E. and Meza, I. (2004) IL8 release, tight junction and cytoskeleton dynamic reorganization conducive to permeability increase are induced by dengue virus infection of microvascular endothelial monolayers. Journal of General Virology, 85, 1801-1813. doi:10.1099/vir.0.19652-0
[41] Bozza, F.A., Cruz, O.G., Zagne, S.M., Azeredo, E.L., Nogueira, R.M., Assis, E.F., Bozza, P.T. and Kubelka, C.F. (2008) Multiplex cytokine profile from dengue patients: MIP-1beta and IFN-gamma as predictive factors for severity. BMC Infectious Diseases, 8, 86. doi:10.1186/1471-2334-8-86
[42] Middleton, J., Patterson, A.M., Gardner, L., Schmutz, C. and Ashton, B.A. (2002) Leukocyte extravasation: Chemokine transport and presentation by the endothelium. Blood, 100, 3853-3860. doi:10.1182/blood.V100.12.3853
[43] Hellier, S., Frodsham, A.J., Hennig, B.J., Klenerman, P., Knapp, S., Ramaley, P., Satsangi, J., Wright, M., Zhang, L., Thomas, H.C., Thursz, M. and Hill, A.V. (2003) Association of genetic variants of the chemokine receptor CCR5 and its ligands, RANTES and MCP-2, with outcome of HCV infection. Hepatology, 38, 1468-1476. doi:10.1016/j.hep.2003.09.027
[44] Morrison, J., Aguirre, S. and Fernandez-Sesma, A. (2012) Innate immunity evasion by Dengue virus. Viruses, 4, 397-413. doi:10.3390/v4030397
[45] Munoz-Jordan, J.L., Sánchez-Burgos, G.G., Laurent-Rolle, M. and García-Sastre, A. (2003) Inhibition of interferon signaling by dengue virus. Proceedings of the National Academy of Sciences of the United States of America, 100, 14333-14338. doi:10.1073/pnas.2335168100
[46] Kawai, T. and Akira, S. (2008) Toll-like receptor and RIG-I-like receptor signaling. Annals of the New York Academy of Sciences, 1143, 1-20. doi:10.1196/annals.1443.020
[47] Akira, S. and Takeda, K. (2004) Toll-like receptor signalling. Nature Reviews Immunology, 4, 499-511.
[48] Ramirez-Ortiz, Z.G., Warke, R.V., Pacheco, L., Xhaja, K., Sarkar, D., Fisher, P.B., Shaw, S.K., Martin, K.J. and Bosch, I. (2006) Discovering innate immunity genes using differential display: A story of RNA helicases. Journal of Cellular Physiology, 209, 636-644. doi:10.1002/jcp.20797
[49] Gale Jr., M. and Foy, E.M. (2005) Evasion of intracellular host defence by hepatitis C virus. Nature, 436, 939-945. doi:10.1038/nature04078

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