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

• These crossreactive T lymphocytes proliferate and produce IFN-gamma after stimulation with a virus strain of another serotype, and demonstrate crossreactive cyotoxic activity against autologous cells infected with heterologous dengue viruses.(ABSTRACT TRUNCATED AT 400 WORDS)[9]
• 4G2 augments dengue virus infection of a human monocytic cell line, U937, which has Fc gamma RI [16].
• A mouse IgG1 anti-dengue virus mAb (3H5) augments dengue virus infection of K562 cells, but a mouse IgG2a anti-dengue virus mAb (4G2) does not [16].
• Monocytes/macrophages (MO/Mphi) are the major target cells for both dengue virus (DV) and bacterial lipopolysaccharide (LPS), and the aim of this study was to define their interactions [20].
• Increased production of interleukin-8 in primary human monocytes and in human epithelial and endothelial cell lines after dengue virus challenge [21].

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

• Ten patients had dengue viruses isolated or detected by PCR, and three had dengue antibody in the CSF [26].
• Isolation of the dengue virus envelope glycoprotein from membranes of infected cells by concanavalin A affinity chromatography [27].
• Analysis of the sequence in the C-PreM-E-NS1 region of the parental dengue type 2 virus (DEN2) New Guinea C (NGC) strain and its mouse-adapted, neurovirulent mutant revealed that 10 nucleotide changes occurred during serial passage in mice [28].
• Enzymatic markers and electron microscopy were utilized to determine the cellular origin of the membrane types isolated from type 2 dengue virus-infected BHK cells by discontinuous sucrose gradient centrifugation [29].
• In cells containing replicons or infected with dengue virus, we found reduced levels of signal transducer and activator of transcription 2 (STAT2), which is a key component of IFN-alpha but not IFN-gamma signaling [24].

References