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The envelope glycoprotein domain III of dengue virus type 2 induced the expression of anticoagulant molecules in endothelial cells

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Abstract

Dengue virus (DV) causes a non-specific febrile illness known as Dengue fever (DF), and a severe life-threatening illness, Dengue hemorrhagic fever/Dengue shock syndrome (DHF/DSS). Hemostatic changes induced by this virus involve three main factors: thrombocytopenia, endothelial cell damage, and significant abnormalities of the coagulation and fibrinolysis systems. The pathogenesis of bleeding in DV infections remains unknown. In this article, we focused on the DV activating endothelial cells and altering the parameters of hemostasis system. The expression of hemostasis-related factors, Thrombomodulin, TF, TFPI, t-PA, and PAI-1, in DV-infected cells were determined by RT-PCR. Flow cytometry analysis and immunofluorescence staining confirmed that the expression levels of TM in the DV-infected HMEC-1 and THP-1 cells were increased. In addition, the purified recombinant domain III of the envelope glycoprotein of DV (EIII) could induce the expression of TM in the HMEC-1 cells and THP-1 cells. The TM expression induced by DV or EIII in the endothelial cells and monocytic cells suggests that the EIII of DV plays an important role in the pathogenesis of DHF/DSS.

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References

  1. Gubler DJ (1998) Dengue and dengue hemorrhagic fever. Clin Microbiol Rev 11:480–496

    CAS  PubMed  Google Scholar 

  2. Leitmeyer KC, Vaughn DW, Watts DM et al (1999) Dengue virus structural differences that correlate with pathogenesis. J Virol 73:4738–4747

    CAS  PubMed  Google Scholar 

  3. Mairuhu AT, Mac Gillavry MR, Setiati TE et al (2003) Is clinical outcome of dengue-virus infections influenced by coagulation and fibrinolysis? A critical review of the evidence. Lancet Infect Dis 3:33–41. doi:10.1016/S1473-3099(03)00487-0

    Article  CAS  PubMed  Google Scholar 

  4. Rice CM, Aebersold R, Teplow DB et al (1986) Partial N-terminal amino acid sequences of three nonstructural proteins of two flaviviruses. Virology 151:1–9

    Article  CAS  PubMed  Google Scholar 

  5. Chambers TJ, Hahn CS, Galler R et al (1990) Flavivirus genome organization, expression, and replication. Annu Rev Microbiol 44:649–688. doi:10.1146/annurev.mi.44.100190.003245

    Article  CAS  PubMed  Google Scholar 

  6. Yaegashi T, Vakharia VN, Page K et al (1986) Partial sequence analysis of cloned dengue virus type 2 genome. Gene 46:257–267

    Article  CAS  PubMed  Google Scholar 

  7. Roehrig JT, Bolin RA, Kelly RG (1998) Monoclonal antibody mapping of the envelope glycoprotein of the dengue 2 virus, Jamaica. Virology 246:317–328. doi:10.1006/viro.1998.9200

    Article  CAS  PubMed  Google Scholar 

  8. Bhardwaj S, Holbrook M, Shope RE et al (2001) Biophysical characterization and vector-specific antagonist activity of domain III of the tick-borne flavivirus envelope protein. J Virol 75:4002–4007. doi:10.1128/JVI.75.8.4002-4007.2001

    Article  CAS  PubMed  Google Scholar 

  9. Lin CW, Wu SC (2003) A functional epitope determinant on domain III of the Japanese encephalitis virus envelope protein interacted with neutralizing-antibody combining sites. J Virol 77:2600–2606

    Article  CAS  PubMed  Google Scholar 

  10. Ni H, Ryman KD, Wang H et al (2000) Interaction of yellow fever virus French neurotropic vaccine strain with monkey brain: characterization of monkey brain membrane receptor escape variants. J Virol 74:2903–2906

    Article  CAS  PubMed  Google Scholar 

  11. Hung JJ, Hsieh MT, Young MJ et al (2004) An external loop region of domain III of dengue virus type 2 envelope protein is involved in serotype-specific binding to mosquito but not mammalian cells. J Virol 78:378–388

    Article  CAS  PubMed  Google Scholar 

  12. Kurane I, Rothman AL, Livingston PG et al (1994) Immunopathologic mechanisms of dengue hemorrhagic fever and dengue shock syndrome. Arch Virol Suppl 9:59–64

    CAS  PubMed  Google Scholar 

  13. Wills BA, Oragui EE, Stephens AC et al (2002) Coagulation abnormalities in dengue hemorrhagic fever: serial investigations in 167 Vietnamese children with dengue shock syndrome. Clin Infect Dis 35:277–285. doi:10.1086/341410

    Article  PubMed  Google Scholar 

  14. Jiang Z, Tang X, Xiao R et al (2007) Dengue virus regulates the expression of hemostasis-related molecules in human vein endothelial cells. J Infect 55:e23–e28. doi:10.1016/j.jinf.2007.04.351

    Article  PubMed  Google Scholar 

  15. Van de Wouwer M, Collen D, Conway EM (2004) Thrombomodulin-protein C-EPCR system: integrated to regulate coagulation and inflammation. Arterioscler Thromb Vasc Biol 24:1374–1383. doi:10.1161/01.ATV.0000134298.25489.92

    Article  PubMed  Google Scholar 

  16. Huang HC, Shi GY, Jiang SJ et al (2003) Thrombomodulin-mediated cell adhesion: involvement of its lectin-like domain. J Biol Chem 278:46750–46759

    Article  CAS  PubMed  Google Scholar 

  17. Bertina RM, Koeleman BP, Koster T et al (1994) Mutation in blood coagulation factor V associated with resistance to activated protein C. Nature 369:64–67

    Article  CAS  PubMed  Google Scholar 

  18. Sakata Y, Curriden S, Lawrence D et al (1985) Activated protein C stimulates the fibrinolytic activity of cultured endothelial cells and decreases antiactivator activity. Proc Natl Acad Sci USA 82:1121–1125

    Article  CAS  PubMed  Google Scholar 

  19. Srichaikul T, Nimmannitya S (2000) Haematology in dengue and dengue haemorrhagic fever. Baillieres Best Pract Res Clin Haematol 13:261–276. doi:10.1053/beha.2000.0073

    CAS  PubMed  Google Scholar 

  20. Ades EW, Candal FJ, Swerlick RA et al (1992) HMEC-1: establishment of an immortalized human microvascular endothelial cell line. J Investig Dermatol 99:683–690

    Article  CAS  PubMed  Google Scholar 

  21. Jaffe EA, Nachman RL, Becker CG et al (1973) Culture of human endothelial cells derived from umbilical veins. Identification by morphologic and immunologic criteria. J Clin Investig 52:2745–2756. doi:10.1172/JCI107470

    Article  CAS  PubMed  Google Scholar 

  22. Peyrefitte CN, Pastorino B, Grau GE et al (2006) Dengue virus infection of human microvascular endothelial cells from different vascular beds promotes both common and specific functional changes. J Med Virol 78:229–242. doi:10.1002/jmv.20532

    Article  CAS  PubMed  Google Scholar 

  23. Camerer E, Kolsto AB, Prydz H (1996) Cell biology of tissue factor, the principal initiator of blood coagulation. Thromb Res 81:1–41

    Article  CAS  PubMed  Google Scholar 

  24. Vassalli JD, Sappino AP, Belin D (1991) The plasminogen activator/plasmin system. J Clin Investig 88:1067–1072. doi:10.1172/JCI115405

    Article  CAS  PubMed  Google Scholar 

  25. Sosothikul D, Seksarn P, Pongsewalak S et al (2007) Activation of endothelial cells, coagulation and fibrinolysis in children with dengue virus infection. Thromb Haemost 97:627–634. doi:10.1160/TH06-02-0094

    CAS  PubMed  Google Scholar 

  26. Dahlback B, Villoutreix BO (2005) Regulation of blood coagulation by the protein C anticoagulant pathway: novel insights into structure–function relationships and molecular recognition. Arterioscler Thromb Vasc Biol 25:1311–1320. doi:10.1161/01.ATV.0000168421.13467.82

    Article  PubMed  Google Scholar 

  27. Butthep P, Chunhakan S, Tangnararatchakit K et al (2006) Elevated soluble thrombomodulin in the febrile stage related to patients at risk for dengue shock syndrome. Pediatr Infect Dis J 25:894–897. doi:10.1097/01.inf.0000237918.85330.b9

    Article  PubMed  Google Scholar 

  28. Huang YH, Lei HY, Liu HS et al (2003) Tissue plasminogen activator induced by dengue virus infection of human endothelial cells. J Med Virol 70:610–616. doi:10.1002/jmv.10438

    Article  CAS  PubMed  Google Scholar 

  29. Krishnamurti C, Peat RA, Cutting MA et al (2002) Platelet adhesion to dengue-2 virus-infected endothelial cells. Am J Trop Med Hyg 66:435–441

    PubMed  Google Scholar 

  30. Van de Wouwer M, Conway EM (2004) Novel functions of thrombomodulin in inflammation. Crit Care Med 32:S254–S261

    Article  PubMed  Google Scholar 

  31. Chin JF, Chu JJ, Ng ML (2007) The envelope glycoprotein domain III of dengue virus serotypes 1 and 2 inhibit virus entry. Microbes Infect 9:1–6. doi:10.1016/j.micinf.2006.09.009

    Article  CAS  PubMed  Google Scholar 

  32. Zhang ZS, Yan YS, Weng YW et al (2007) High-level expression of recombinant dengue virus type 2 envelope domain III protein and induction of neutralizing antibodies in BALB/C mice. J Virol Methods 143:125–131. doi:10.1016/j.jviromet.2007.02.012

    Article  CAS  PubMed  Google Scholar 

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Acknowledgments

We would like to thank Dr. H. L. Wang for her critical reading of the manuscript. This study was supported in part by a research grant NSC-98-2320-B-242-001-MY3 from the National Science Council, Taiwan.

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Authors and Affiliations

  1. Department of Health, Bureau of Foods and Drug Analysis, Tainan, Taiwan, ROC

    Lien-Cheng Chen

  2. Department of Medical Laboratory Sciences and Biotechnology, College of Medicine, National Cheng Kung University, Tainan, Taiwan, ROC

    Trai-Ming Yeh

  3. 5th Branch Office, Center for Disease Control, Kaohsiung, Taiwan, ROC

    Yi-Ying Lin

  4. Department of Medical Technology, Fooyin University, Kaohsiung Hsien 831, Taiwan, ROC

    Yi-Ying Lin, Yi-Fen Wang, Shu-Jem Su, Chang-Yu Chen, Kuan-Hua Lin, Miao-Chen Chou & Huey-Wen Shyu

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  1. Lien-Cheng Chen
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Correspondence to Huey-Wen Shyu.

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Chen, LC., Yeh, TM., Lin, YY. et al. The envelope glycoprotein domain III of dengue virus type 2 induced the expression of anticoagulant molecules in endothelial cells. Mol Cell Biochem 342, 215–221 (2010). https://doi.org/10.1007/s11010-010-0486-6

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  • DOI: https://doi.org/10.1007/s11010-010-0486-6

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