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MeSH Review


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Disease relevance of Dengue

  • These viruses generally cause a benign syndrome, dengue fever, in the American and African tropics, and a severe syndrome, dengue hemorrhagic fever/dengue shock syndrome (DHF/DSS), in Southeast Asian children [1].
  • A region of the predicted polyprotein sequence was found to share similarity with a nonstructural protein encoded by dengue virus, a member of the flavivirus family [2].
  • It was also noted that cells pretreated with antibodies against alpha(v)beta(3) integrin can effectively inhibit flavivirus Japanese encephalitis but to a lesser extent flavivirus dengue infections [3].
  • Proliferative responses to PHA, anti-CD3, tetanus toxoid, and dengue Ags were decreased significantly in PBMC obtained during the acute infection [4].
  • We analyzed the CD4+ T-lymphocyte responses to dengue, West Nile, and yellow fever viruses 4 months after immunization of a volunteer with an experimental live-attenuated dengue virus type 1 vaccine (DEN-1 45AZ5) [5].

High impact information on Dengue

  • Cryo-EM reconstruction of dengue virus in complex with the carbohydrate recognition domain of DC-SIGN [6].
  • Heparin, highly sulfated heparan sulfate, and the polysulfonate pharmaceutical Suramin effectively prevented dengue virus infection of target cells, indicating that the envelope protein-target cell receptor interaction is a critical determinant of infectivity [7].
  • THP-1 cells become susceptible to dengue infection after transfection of DC-specific ICAM-3 grabbing nonintegrin (DC-SIGN), or its homologue L-SIGN, whereas the infection of dendritic cells is blocked by anti-DC-SIGN antibodies and not by antibodies to other molecules on these cells [8].
  • Serotype crossreactive clones produced high titers of IFN-gamma after stimulation with dengue 3 antigens, and also produced IFN-gamma to lower levels after stimulation with dengue 1, 2, and 4 antigens [9].
  • The culture fluids obtained from PBL exposed to autologous DV-monocytes, which contained high IFN activity, completely inhibited dengue virus infection of monocytes [10].

Chemical compound and disease context of Dengue

  • We found that the cellular receptor utilized by dengue envelope protein to bind to target cells is a highly sulfated type of heparan sulfate [7].
  • A ligand-binding pocket in the dengue virus envelope glycoprotein [11].
  • To understand this mechanism, a viral replicase assay that utilizes extracts from dengue virus-infected mosquito (C6/36) cells and exogenous viral RNA templates is reported in this study [12].
  • Dengue virus type 2 NS3, a multifunctional protein, has a serine protease domain (NS3pro) that requires the conserved hydrophilic domain of NS2B for protease activity in cleavage of the polyprotein precursor at sites following two basic amino acids [13].
  • A structural basis for the inhibition of the NS5 dengue virus mRNA 2'-O-methyltransferase domain by ribavirin 5'-triphosphate [14].

Biological context of Dengue

  • The cells that proliferate in the dengue antigen-stimulated bulk cultures have CD3+, CD4+, CD8-, CD16-, and CD20- phenotypes [15].
  • This is caused by the uptake of dengue virus-antibody complexes by Fc gamma R. We previously reported that Fc gamma RI can mediate antibody-dependent enhancement [16].
  • The full-length premembrane (prM) coding region of the dengue virus type 2 (DEN-2; Jamaica) genome was expressed in C6/36 (Aedes albopictus) cells in either the sense or the antisense orientation from a double subgenomic Sindbis (dsSIN) virus [17].
  • Mutagenesis of the NS3 protease of dengue virus type 2 [18].
  • Activation of the dengue virus-infected DCs was blunted compared to the surrounding, uninfected DCs, and dengue virus infection induced low-level release of interleukin-12 p70 (IL-12 p70), a key cytokine in the development of cell-mediated immunity (CMI) [19].

Anatomical context of Dengue


Gene context of Dengue

  • A variant in the CD209 promoter is associated with severity of dengue disease [22].
  • Critical roles for both STAT1-dependent and STAT1-independent pathways in the control of primary dengue virus infection in mice [23].
  • As elevated interleukin-8 (IL-8) levels have been observed in sera from patients with more severe disease manifestations, a study was initiated to look at the effect of dengue virus infection in vitro on proinflammatory cytokine secretion and expression [21].
  • Dengue virus inhibits alpha interferon signaling by reducing STAT2 expression [24].
  • Recruitment and activation of potential target cells to sites of DEN2V replication by virus-induced chemokine production may contribute to viral replication as well as to the inflammatory components of dengue virus disease [25].

Analytical, diagnostic and therapeutic context of Dengue


  1. Pathogenesis of dengue: challenges to molecular biology. Halstead, S.B. Science (1988) [Pubmed]
  2. Hepatitis C virus shares amino acid sequence similarity with pestiviruses and flaviviruses as well as members of two plant virus supergroups. Miller, R.H., Purcell, R.H. Proc. Natl. Acad. Sci. U.S.A. (1990) [Pubmed]
  3. Interaction of West Nile virus with alpha v beta 3 integrin mediates virus entry into cells. Chu, J.J., Ng, M.L. J. Biol. Chem. (2004) [Pubmed]
  4. Impaired T cell proliferation in acute dengue infection. Mathew, A., Kurane, I., Green, S., Vaughn, D.W., Kalayanarooj, S., Suntayakorn, S., Ennis, F.A., Rothman, A.L. J. Immunol. (1999) [Pubmed]
  5. Dengue virus-specific human CD4+ T-lymphocyte responses in a recipient of an experimental live-attenuated dengue virus type 1 vaccine: bulk culture proliferation, clonal analysis, and precursor frequency determination. Green, S., Kurane, I., Edelman, R., Tacket, C.O., Eckels, K.H., Vaughn, D.W., Hoke, C.H., Ennis, F.A. J. Virol. (1993) [Pubmed]
  6. Cryo-EM reconstruction of dengue virus in complex with the carbohydrate recognition domain of DC-SIGN. Pokidysheva, E., Zhang, Y., Battisti, A.J., Bator-Kelly, C.M., Chipman, P.R., Xiao, C., Gregorio, G.G., Hendrickson, W.A., Kuhn, R.J., Rossmann, M.G. Cell (2006) [Pubmed]
  7. Dengue virus infectivity depends on envelope protein binding to target cell heparan sulfate. Chen, Y., Maguire, T., Hileman, R.E., Fromm, J.R., Esko, J.D., Linhardt, R.J., Marks, R.M. Nat. Med. (1997) [Pubmed]
  8. DC-SIGN (CD209) mediates dengue virus infection of human dendritic cells. Tassaneetrithep, B., Burgess, T.H., Granelli-Piperno, A., Trumpfheller, C., Finke, J., Sun, W., Eller, M.A., Pattanapanyasat, K., Sarasombath, S., Birx, D.L., Steinman, R.M., Schlesinger, S., Marovich, M.A. J. Exp. Med. (2003) [Pubmed]
  9. Dengue virus-specific human T cell clones. Serotype crossreactive proliferation, interferon gamma production, and cytotoxic activity. Kurane, I., Meager, A., Ennis, F.A. J. Exp. Med. (1989) [Pubmed]
  10. Induction of interferon alpha from human lymphocytes by autologous, dengue virus-infected monocytes. Kurane, I., Ennis, F.A. J. Exp. Med. (1987) [Pubmed]
  11. A ligand-binding pocket in the dengue virus envelope glycoprotein. Modis, Y., Ogata, S., Clements, D., Harrison, S.C. Proc. Natl. Acad. Sci. U.S.A. (2003) [Pubmed]
  12. A novel in vitro replication system for Dengue virus. Initiation of RNA synthesis at the 3'-end of exogenous viral RNA templates requires 5'- and 3'-terminal complementary sequence motifs of the viral RNA. You, S., Padmanabhan, R. J. Biol. Chem. (1999) [Pubmed]
  13. Purified NS2B/NS3 serine protease of dengue virus type 2 exhibits cofactor NS2B dependence for cleavage of substrates with dibasic amino acids in vitro. Yusof, R., Clum, S., Wetzel, M., Murthy, H.M., Padmanabhan, R. J. Biol. Chem. (2000) [Pubmed]
  14. A structural basis for the inhibition of the NS5 dengue virus mRNA 2'-O-methyltransferase domain by ribavirin 5'-triphosphate. Benarroch, D., Egloff, M.P., Mulard, L., Guerreiro, C., Romette, J.L., Canard, B. J. Biol. Chem. (2004) [Pubmed]
  15. Human T cell responses to dengue virus antigens. Proliferative responses and interferon gamma production. Kurane, I., Innis, B.L., Nisalak, A., Hoke, C., Nimmannitya, S., Meager, A., Ennis, F.A. J. Clin. Invest. (1989) [Pubmed]
  16. Human IgG Fc receptor II mediates antibody-dependent enhancement of dengue virus infection. Littaua, R., Kurane, I., Ennis, F.A. J. Immunol. (1990) [Pubmed]
  17. Pathogen-derived resistance to dengue type 2 virus in mosquito cells by expression of the premembrane coding region of the viral genome. Gaines, P.J., Olson, K.E., Higgs, S., Powers, A.M., Beaty, B.J., Blair, C.D. J. Virol. (1996) [Pubmed]
  18. Mutagenesis of the NS3 protease of dengue virus type 2. Valle, R.P., Falgout, B. J. Virol. (1998) [Pubmed]
  19. Human dendritic cells are activated by dengue virus infection: enhancement by gamma interferon and implications for disease pathogenesis. Libraty, D.H., Pichyangkul, S., Ajariyakhajorn, C., Endy, T.P., Ennis, F.A. J. Virol. (2001) [Pubmed]
  20. Bacterial lipopolysaccharide inhibits dengue virus infection of primary human monocytes/macrophages by blockade of virus entry via a CD14-dependent mechanism. Chen, Y.C., Wang, S.Y., King, C.C. J. Virol. (1999) [Pubmed]
  21. Increased production of interleukin-8 in primary human monocytes and in human epithelial and endothelial cell lines after dengue virus challenge. Bosch, I., Xhaja, K., Estevez, L., Raines, G., Melichar, H., Warke, R.V., Fournier, M.V., Ennis, F.A., Rothman, A.L. J. Virol. (2002) [Pubmed]
  22. A variant in the CD209 promoter is associated with severity of dengue disease. Sakuntabhai, A., Turbpaiboon, C., Casadémont, I., Chuansumrit, A., Lowhnoo, T., Kajaste-Rudnitski, A., Kalayanarooj, S.M., Tangnararatchakit, K., Tangthawornchaikul, N., Vasanawathana, S., Chaiyaratana, W., Yenchitsomanus, P.T., Suriyaphol, P., Avirutnan, P., Chokephaibulkit, K., Matsuda, F., Yoksan, S., Jacob, Y., Lathrop, G.M., Malasit, P., Desprès, P., Julier, C. Nat. Genet. (2005) [Pubmed]
  23. Critical roles for both STAT1-dependent and STAT1-independent pathways in the control of primary dengue virus infection in mice. Shresta, S., Sharar, K.L., Prigozhin, D.M., Snider, H.M., Beatty, P.R., Harris, E. J. Immunol. (2005) [Pubmed]
  24. Dengue virus inhibits alpha interferon signaling by reducing STAT2 expression. Jones, M., Davidson, A., Hibbert, L., Gruenwald, P., Schlaak, J., Ball, S., Foster, G.R., Jacobs, M. J. Virol. (2005) [Pubmed]
  25. Dengue virus nonstructural protein NS5 induces interleukin-8 transcription and secretion. Medin, C.L., Fitzgerald, K.A., Rothman, A.L. J. Virol. (2005) [Pubmed]
  26. Neurological manifestations of dengue infection. Solomon, T., Dung, N.M., Vaughn, D.W., Kneen, R., Thao, L.T., Raengsakulrach, B., Loan, H.T., Day, N.P., Farrar, J., Myint, K.S., Warrell, M.J., James, W.S., Nisalak, A., White, N.J. Lancet (2000) [Pubmed]
  27. Isolation of the dengue virus envelope glycoprotein from membranes of infected cells by concanavalin A affinity chromatography. Stohlman, S.A., Eylar, O.R., Wisseman, C.L. J. Virol. (1976) [Pubmed]
  28. Genetic determinants responsible for acquisition of dengue type 2 virus mouse neurovirulence. Bray, M., Men, R., Tokimatsu, I., Lai, C.J. J. Virol. (1998) [Pubmed]
  29. Dengue virus-induced modifications of host cell membranes. Stohlman, S.A., Wisseman, C.L., Eylar, O.R., Silverman, D.J. J. Virol. (1975) [Pubmed]
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