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Published in: Virology Journal 1/2011

Open Access 01-12-2011 | Research

Japanese encephalitis virus infection induces changes of mRNA profile of mouse spleen and brain

Authors: Yang Yang, Jing Ye, Xiaohong Yang, Rong Jiang, Huanchun Chen, Shengbo Cao

Published in: Virology Journal | Issue 1/2011

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Abstract

Background

Japanese encephalitis virus (JEV) is a mosquito-borne flavivirus, leading to an acute encephalitis and damage to the central nervous system (CNS). The mechanism of JEV pathogenesis is still unclear. DNA microarray analyses have been recently employed to detect changes in host gene expression, which is helpful to reveal molecular pathways that govern viral pathogenesis. In order to globally identify candidate host genes associated with JEV pathogenesis, a systematic mRNA profiling was performed in spleens and brains of JEV-infected mice.

Results

The results of microarray analysis showed that 437 genes in spleen and 1119 genes in brain were differentially expressed in response to JEV infection, with obviously upregulated genes like pro-inflammatory chemokines and cytokines, apoptosis-related proteases and IFN inducible transcription factors. And the significant pathways of differentially expressed genes are involved in cytokine-cytokine receptor interaction, natural killer cell mediated cytotoxicity, antigen processing and presentation, MAPK signaling, and toll-like receptor signaling, etc. The differential expression of these genes suggests a strong antiviral response of host but may also contribute to the pathogenesis of JEV resulting in encephalitis. Quantitative RT-PCR (RT-qPCR) assay of some selected genes further confirmed the results of microarray assay.

Conclusions

Data obtained from mRNA microarray suggests that JEV infection causes significant changes of mRNA expression profiles in mouse spleen and brain. Most of differentially expression genes are associated with antiviral response of host, which may provide important information for investigation of JEV pathogenesis and therapeutic method.
Appendix
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Literature
1.
go back to reference Hanna JN, Ritchie SA, Phillips DA, Shield J, Bailey MC, Mackenzie JS, Poidinger M, McCall BJ, Mills PJ: An outbreak of Japanese encephalitis in the Torres Strait, Australia, 1995. Med J Aus t 1996, 165: 256-260. Hanna JN, Ritchie SA, Phillips DA, Shield J, Bailey MC, Mackenzie JS, Poidinger M, McCall BJ, Mills PJ: An outbreak of Japanese encephalitis in the Torres Strait, Australia, 1995. Med J Aus t 1996, 165: 256-260.
3.
go back to reference World Health Organization: Manual for the Laboratory Diagnosis of Japanese Encephalitis Virus Infection. 2007. World Health Organization: Manual for the Laboratory Diagnosis of Japanese Encephalitis Virus Infection. 2007.
4.
go back to reference Vaughn DW, Hoke CH: The epidemiology of Japanese encephalitis: prospects for prevention. Epidemiol Rev 1992, 14: 197-221.PubMed Vaughn DW, Hoke CH: The epidemiology of Japanese encephalitis: prospects for prevention. Epidemiol Rev 1992, 14: 197-221.PubMed
5.
go back to reference Yang KD, Yeh WT, Chen RF: A model to study neurotropism and persistency of Japanese encephalitis virus infection in human neuroblastoma cells and leukocytes. J Gen Virol 2004, 85: 635-642.CrossRefPubMed Yang KD, Yeh WT, Chen RF: A model to study neurotropism and persistency of Japanese encephalitis virus infection in human neuroblastoma cells and leukocytes. J Gen Virol 2004, 85: 635-642.CrossRefPubMed
6.
go back to reference Aleyas AG, George JA, Han YW: Functional modulation of dendritic cells and macrophages by Japanese encephalitis virus through MyD88 adaptor molecule-dependent and - independent pathways. J Immunol 2009, 183: 2462-2474.CrossRefPubMed Aleyas AG, George JA, Han YW: Functional modulation of dendritic cells and macrophages by Japanese encephalitis virus through MyD88 adaptor molecule-dependent and - independent pathways. J Immunol 2009, 183: 2462-2474.CrossRefPubMed
7.
go back to reference Wolinsky JS: Subacute sclerosing panencephalitis progressive rubella panencephalitis, and multifocal leukoencephelapathy. In Immunological mechanisms in neurologic and psychiatric disease. Edited by: Waksman BH. New York: Raven Press; 1990:259-268. Wolinsky JS: Subacute sclerosing panencephalitis progressive rubella panencephalitis, and multifocal leukoencephelapathy. In Immunological mechanisms in neurologic and psychiatric disease. Edited by: Waksman BH. New York: Raven Press; 1990:259-268.
8.
go back to reference Warke RV, Xhaja K, Martin KJ: Dengue virus induces novel changes in gene expression of human umbilical vein endothelial cells. J Virol 2003, 77: 11822-11832.PubMedCentralCrossRefPubMed Warke RV, Xhaja K, Martin KJ: Dengue virus induces novel changes in gene expression of human umbilical vein endothelial cells. J Virol 2003, 77: 11822-11832.PubMedCentralCrossRefPubMed
9.
go back to reference Fredericksen BL, Smith M, Katze MG: The host response to West Nile Virus infection limits viral spread through the activation of the interferon regulatory factor 3 pathway. J Virol 2004, 78: 7737-7747.PubMedCentralCrossRefPubMed Fredericksen BL, Smith M, Katze MG: The host response to West Nile Virus infection limits viral spread through the activation of the interferon regulatory factor 3 pathway. J Virol 2004, 78: 7737-7747.PubMedCentralCrossRefPubMed
11.
go back to reference Gupta N, Santhosh SR, Babu JP, Parida MM, Rao PV: Chemokine profiling of Japanese encephalitis virus-infected mouse neuroblastoma cells by microarray and real-time RT-PCR: Implication in neuropathogenesis. Virus Research 2010, 147: 107-112.CrossRefPubMed Gupta N, Santhosh SR, Babu JP, Parida MM, Rao PV: Chemokine profiling of Japanese encephalitis virus-infected mouse neuroblastoma cells by microarray and real-time RT-PCR: Implication in neuropathogenesis. Virus Research 2010, 147: 107-112.CrossRefPubMed
12.
go back to reference Biswas SM, Kar S, Singh R, Chakraborty D, Vipat V, Raut CG, Mishra AC, Gore MM, Ghosh D: Immunomodulatory Cytokines Determine the Outcome of Japanese Encephalitis Virus Infection in Mice. Journal of Medical Virology 2010, 82: 304-310.CrossRefPubMed Biswas SM, Kar S, Singh R, Chakraborty D, Vipat V, Raut CG, Mishra AC, Gore MM, Ghosh D: Immunomodulatory Cytokines Determine the Outcome of Japanese Encephalitis Virus Infection in Mice. Journal of Medical Virology 2010, 82: 304-310.CrossRefPubMed
13.
go back to reference Sakurai-Yamashita Y, Shigematsu K, Yamashita K: Expression of MCP-1 in the hippocampus of SHRSP with ischemia-related delayed neuronal death. Cell Mol Neurobiol 2006, 26: 823-831.CrossRefPubMed Sakurai-Yamashita Y, Shigematsu K, Yamashita K: Expression of MCP-1 in the hippocampus of SHRSP with ischemia-related delayed neuronal death. Cell Mol Neurobiol 2006, 26: 823-831.CrossRefPubMed
14.
go back to reference Hsieh MF, Lai SL, Chen JP: Both CXCR3 and CXCL10/IFN-inducible protein 10 are required for resistance to primary infection by dengue virus. J Immunol 2006, 177: 1855-1863.CrossRefPubMed Hsieh MF, Lai SL, Chen JP: Both CXCR3 and CXCL10/IFN-inducible protein 10 are required for resistance to primary infection by dengue virus. J Immunol 2006, 177: 1855-1863.CrossRefPubMed
15.
go back to reference Hardison JL, Wrightsman RA, Carpenter PM: The chemokines CXCL9 and CXCL10 promote a protective immune response but do not contribute to cardiac inflammation following infection with Trypanosoma cruzi. Infect Immun 2006, 74: 125-134.PubMedCentralCrossRefPubMed Hardison JL, Wrightsman RA, Carpenter PM: The chemokines CXCL9 and CXCL10 promote a protective immune response but do not contribute to cardiac inflammation following infection with Trypanosoma cruzi. Infect Immun 2006, 74: 125-134.PubMedCentralCrossRefPubMed
17.
go back to reference Marietjie V, Timothy GM, Michael AW, Thomas JK, Janusz TP, Felicity JB, Patricia AL, Robert S: Gene expression in mice infected with West Nile virus strains of different neurovirulence. Virology 2005, 119-140. Marietjie V, Timothy GM, Michael AW, Thomas JK, Janusz TP, Felicity JB, Patricia AL, Robert S: Gene expression in mice infected with West Nile virus strains of different neurovirulence. Virology 2005, 119-140.
18.
go back to reference Chang TH, Liao CL, Lin YL: Flavivirus induces interferon-beta gene expression through a pathway involving RIG-I-dependent IRF-3 and PI3K-dependent NF-kappaB activation. Microbes Infect 2006, 8: 157-71.CrossRefPubMed Chang TH, Liao CL, Lin YL: Flavivirus induces interferon-beta gene expression through a pathway involving RIG-I-dependent IRF-3 and PI3K-dependent NF-kappaB activation. Microbes Infect 2006, 8: 157-71.CrossRefPubMed
19.
go back to reference Nakajima H, Park HL, Henkart PA: Synergistic roles of granzymes A and B in mediating target cell death by rat basophilic leukemia mast cell tumors also expressing cytolysin/perforin. J Exp Med 1995, 181: 1037-1046.CrossRefPubMed Nakajima H, Park HL, Henkart PA: Synergistic roles of granzymes A and B in mediating target cell death by rat basophilic leukemia mast cell tumors also expressing cytolysin/perforin. J Exp Med 1995, 181: 1037-1046.CrossRefPubMed
20.
go back to reference Browne KA, Blink E, Sutton VR: Cytosolic delivery of granzyme B by bacterial toxins: evidence that endosomal disruption, in addition to transmembrane pore formation, is an important function of perforin. Mol Cell Biol 1999, 19: 8604-8615.PubMedCentralCrossRefPubMed Browne KA, Blink E, Sutton VR: Cytosolic delivery of granzyme B by bacterial toxins: evidence that endosomal disruption, in addition to transmembrane pore formation, is an important function of perforin. Mol Cell Biol 1999, 19: 8604-8615.PubMedCentralCrossRefPubMed
21.
go back to reference Young JD, Hengartner H, Podack ER: Purification and characterization of a cytolytic pore-forming protein from granules of cloned lymphocytes with natural killer activity. Cell 1986, 44: 849-859.CrossRefPubMed Young JD, Hengartner H, Podack ER: Purification and characterization of a cytolytic pore-forming protein from granules of cloned lymphocytes with natural killer activity. Cell 1986, 44: 849-859.CrossRefPubMed
22.
go back to reference Joseph AT, Phillip IB: A renaissance in understanding the multiple and diverse functions of Granzymes? Immunity 2008, 29: 665-667.CrossRef Joseph AT, Phillip IB: A renaissance in understanding the multiple and diverse functions of Granzymes? Immunity 2008, 29: 665-667.CrossRef
23.
go back to reference Lin RJ, Liao CL, Lin YL: Replication-incompetent virions of Japanese encephalitis virus trigger neuronal cell death by oxidative stress in a culture system. J Gen Virol 2004, 85: 521-533.CrossRefPubMed Lin RJ, Liao CL, Lin YL: Replication-incompetent virions of Japanese encephalitis virus trigger neuronal cell death by oxidative stress in a culture system. J Gen Virol 2004, 85: 521-533.CrossRefPubMed
24.
go back to reference Tsao CH, Su HL, Lin YL: Japanese encephalitis virus infection activates caspase-8 and -9 in a FADD-independent and mitochondrion-dependent manner. J Gen Virol 2008, 89: 1930-1941.CrossRefPubMed Tsao CH, Su HL, Lin YL: Japanese encephalitis virus infection activates caspase-8 and -9 in a FADD-independent and mitochondrion-dependent manner. J Gen Virol 2008, 89: 1930-1941.CrossRefPubMed
25.
go back to reference Yang TC, Shiu SL, Chuang PH, Lin YJ, Wan L, Lan YC, Lin CW: Japanese encephalitis virus NS2B-NS3 protease induces caspase 3 activation and mitochondria-mediated apoptosis in human medulloblastoma cells. Virus Research 2009, 143: 77-85.CrossRefPubMed Yang TC, Shiu SL, Chuang PH, Lin YJ, Wan L, Lan YC, Lin CW: Japanese encephalitis virus NS2B-NS3 protease induces caspase 3 activation and mitochondria-mediated apoptosis in human medulloblastoma cells. Virus Research 2009, 143: 77-85.CrossRefPubMed
26.
go back to reference Martinon F, Tschopp J: "Inflammatory caspases and inflammasomes: master switches of inflammation". Cell Death Differ 2007, 14: 10-22.CrossRefPubMed Martinon F, Tschopp J: "Inflammatory caspases and inflammasomes: master switches of inflammation". Cell Death Differ 2007, 14: 10-22.CrossRefPubMed
28.
go back to reference Meulen J, Sakho M, Koulemou K: Activation of the cytokine network and unfavorable outcome in patients with yellow fever. J Infect Dis 2004, 190: 1821-1827.CrossRefPubMed Meulen J, Sakho M, Koulemou K: Activation of the cytokine network and unfavorable outcome in patients with yellow fever. J Infect Dis 2004, 190: 1821-1827.CrossRefPubMed
29.
go back to reference Cartmell T, Poole S, Turnbull AV: Circulating interleukin-6 mediates the febrile response to localized inflammation in rats. J Physiol 2000, 526: 653-661.PubMedCentralCrossRefPubMed Cartmell T, Poole S, Turnbull AV: Circulating interleukin-6 mediates the febrile response to localized inflammation in rats. J Physiol 2000, 526: 653-661.PubMedCentralCrossRefPubMed
30.
go back to reference Lucas M, Mashimo T, Frenkiel MP: Infection of mouse neurones by West Nile virus is modulated by the interferoninducible 2V-5V oligoadenylate synthetase 1b protein. Immunol Cell Biol 2003, 81: 230-236.CrossRefPubMed Lucas M, Mashimo T, Frenkiel MP: Infection of mouse neurones by West Nile virus is modulated by the interferoninducible 2V-5V oligoadenylate synthetase 1b protein. Immunol Cell Biol 2003, 81: 230-236.CrossRefPubMed
31.
go back to reference Mashimo T, Lucas M, Simon-Chazottes D: A nonsense mutation in the gene encoding 2V-5V-oligoadenylate synthetase/L1 isoform is associated with West Nile virus susceptibility in laboratory mice. Proc Natl Acad Sci USA 2002, 99: 11311-11316.PubMedCentralCrossRefPubMed Mashimo T, Lucas M, Simon-Chazottes D: A nonsense mutation in the gene encoding 2V-5V-oligoadenylate synthetase/L1 isoform is associated with West Nile virus susceptibility in laboratory mice. Proc Natl Acad Sci USA 2002, 99: 11311-11316.PubMedCentralCrossRefPubMed
33.
go back to reference Lin RJ, Yu HP, Chang BL: Distinct antiviral roles for human 2',5'-oligoadenylate synthetase family members a gainst dengue virus infection. J Immunol 2009, 183: 8035-43.CrossRefPubMed Lin RJ, Yu HP, Chang BL: Distinct antiviral roles for human 2',5'-oligoadenylate synthetase family members a gainst dengue virus infection. J Immunol 2009, 183: 8035-43.CrossRefPubMed
34.
go back to reference Saha S, Rangarajan PN: Common host genes are activated in mouse brain by Japanese encephalitis and rabies viruses. Journal of General Virology 2003, 84: 1729-1735.CrossRefPubMed Saha S, Rangarajan PN: Common host genes are activated in mouse brain by Japanese encephalitis and rabies viruses. Journal of General Virology 2003, 84: 1729-1735.CrossRefPubMed
35.
go back to reference Borda JT, Alvarez X, Mohan M, Hasegawa A, Bernardino A, Jean S, Aye P, Lackner AA: CD163, a marker of perivascular macrophages, is up-regulated by microglia in Simian immunodeficiency Virus Encephalitis after Haptoglobin-Hemoglobin Complex stimulation and is suggestive of breakdown of the Blood-Brain Barrier. The American Journal of Pathology 2008, 172: 725-737.PubMedCentralCrossRefPubMed Borda JT, Alvarez X, Mohan M, Hasegawa A, Bernardino A, Jean S, Aye P, Lackner AA: CD163, a marker of perivascular macrophages, is up-regulated by microglia in Simian immunodeficiency Virus Encephalitis after Haptoglobin-Hemoglobin Complex stimulation and is suggestive of breakdown of the Blood-Brain Barrier. The American Journal of Pathology 2008, 172: 725-737.PubMedCentralCrossRefPubMed
36.
go back to reference Kim WK, Alvarez X, Fisher J, Bronfin B, Westmoreland S, McLaurin J, Williams K: CD163 identifies perivascular macrophages in normal and viral encephalitic brains and potential precursors to perivascular macrophages in blood. American Journal of Pathology 2006, 168: 822-834.PubMedCentralCrossRefPubMed Kim WK, Alvarez X, Fisher J, Bronfin B, Westmoreland S, McLaurin J, Williams K: CD163 identifies perivascular macrophages in normal and viral encephalitic brains and potential precursors to perivascular macrophages in blood. American Journal of Pathology 2006, 168: 822-834.PubMedCentralCrossRefPubMed
Metadata
Title
Japanese encephalitis virus infection induces changes of mRNA profile of mouse spleen and brain
Authors
Yang Yang
Jing Ye
Xiaohong Yang
Rong Jiang
Huanchun Chen
Shengbo Cao
Publication date
01-12-2011
Publisher
BioMed Central
Published in
Virology Journal / Issue 1/2011
Electronic ISSN: 1743-422X
DOI
https://doi.org/10.1186/1743-422X-8-80

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