flavivirus polyprotein gene


Gene Symbol: flavivirus polyprotein gene
Description: flavivirus polyprotein
Species: Dengue virus 2
Products:     flavivirus polyprotein gene

Top Publications

  1. Sánchez I, Ruiz B. A single nucleotide change in the E protein gene of dengue virus 2 Mexican strain affects neurovirulence in mice. J Gen Virol. 1996;77 ( Pt 10):2541-5 pubmed
    ..This substitution falls in domain III of the E protein, which plays an important role in viral binding; therefore, we propose that the substitution affects virulence and cellular tropism. ..
  2. Bielefeldt Ohmann H. Analysis of antibody-independent binding of dengue viruses and dengue virus envelope protein to human myelomonocytic cells and B lymphocytes. Virus Res. 1998;57:63-79 pubmed
  3. Modis Y, Ogata S, Clements D, Harrison S. A ligand-binding pocket in the dengue virus envelope glycoprotein. Proc Natl Acad Sci U S A. 2003;100:6986-91 pubmed
    ..These features point to a structural pathway for the fusion-activating transition and suggest a strategy for finding small-molecule inhibitors of dengue and other flaviviruses. ..
  4. Sakoonwatanyoo P, Boonsanay V, Smith D. Growth and production of the dengue virus in C6/36 cells and identification of a laminin-binding protein as a candidate serotype 3 and 4 receptor protein. Intervirology. 2006;49:161-72 pubmed
    ..The results suggest that multiple receptors may be used by the dengue virus to enter into insect cells, and that one of these proteins may be a laminin-binding protein. ..
  5. Hsieh S, Tsai W, Wang W. The length of and nonhydrophobic residues in the transmembrane domain of dengue virus envelope protein are critical for its retention and assembly in the endoplasmic reticulum. J Virol. 2010;84:4782-97 pubmed publisher
  6. Yap T, Xu T, Chen Y, Malet H, Egloff M, Canard B, et al. Crystal structure of the dengue virus RNA-dependent RNA polymerase catalytic domain at 1.85-angstrom resolution. J Virol. 2007;81:4753-65 pubmed
    ..In the absence of a template strand, a chain-terminating nucleoside analogue binds to the priming loop site. These results should inform and accelerate the structure-based design of antiviral compounds against dengue virus. ..
  7. Filomatori C, Iglesias N, Villordo S, Alvarez D, Gamarnik A. RNA sequences and structures required for the recruitment and activity of the dengue virus polymerase. J Biol Chem. 2011;286:6929-39 pubmed publisher
    ..We propose that the long range RNA-RNA interactions in the viral genome play multiple roles during RNA synthesis. Together, we provide new molecular details about the promoter-dependent dengue virus RNA polymerase activity. ..
  8. Kanai R, Kar K, Anthony K, Gould L, Ledizet M, Fikrig E, et al. Crystal structure of west nile virus envelope glycoprotein reveals viral surface epitopes. J Virol. 2006;80:11000-8 pubmed
    ..By revealing the details of the molecular landscape of the West Nile virus surface, our structure will assist the design of antiviral vaccines and therapeutics. ..
  9. Falconar A. Identification of an epitope on the dengue virus membrane (M) protein defined by cross-protective monoclonal antibodies: design of an improved epitope sequence based on common determinants present in both envelope (E and M) proteins. Arch Virol. 1999;144:2313-30 pubmed
    ..These peptide sequence will now be tested for their ability to generate cross-protective antibodies against each dengue virus serotype when delivered with appropriate T-helper epitopes. ..

More Information


  1. Li H, Clum S, You S, Ebner K, Padmanabhan R. The serine protease and RNA-stimulated nucleoside triphosphatase and RNA helicase functional domains of dengue virus type 2 NS3 converge within a region of 20 amino acids. J Virol. 1999;73:3108-16 pubmed
  2. Wang S, He R, Anderson R. PrM- and cell-binding domains of the dengue virus E protein. J Virol. 1999;73:2547-51 pubmed
  3. Libraty D, Young P, Pickering D, Endy T, Kalayanarooj S, Green S, et al. High circulating levels of the dengue virus nonstructural protein NS1 early in dengue illness correlate with the development of dengue hemorrhagic fever. J Infect Dis. 2002;186:1165-8 pubmed publisher
    ..An elevated free sNS1 level (> or =600 ng/mL) within 72 h of illness onset identified patients at risk for developing DHF...
  4. Avirutnan P, Punyadee N, Noisakran S, Komoltri C, Thiemmeca S, Auethavornanan K, et al. Vascular leakage in severe dengue virus infections: a potential role for the nonstructural viral protein NS1 and complement. J Infect Dis. 2006;193:1078-88 pubmed publisher
    ..Complement activation mediated by NS1 leads to local and systemic generation of anaphylatoxins and SC5b-9, which may contribute to the pathogenesis of the vascular leakage that occurs in patients with DHF/DSS...
  5. Mukhopadhyay S, Kuhn R, Rossmann M. A structural perspective of the flavivirus life cycle. Nat Rev Microbiol. 2005;3:13-22 pubmed publisher
    ..This review focuses mainly on structural studies of dengue virus...
  6. Xu T, Sampath A, Chao A, Wen D, Nanao M, Chene P, et al. Structure of the Dengue virus helicase/nucleoside triphosphatase catalytic domain at a resolution of 2.4 A. J Virol. 2005;79:10278-88 pubmed
    ..A possible model for the unwinding mechanism is proposed. ..
  7. Tassaneetrithep B, Burgess T, Granelli Piperno A, Trumpfheller C, Finke J, Sun W, et al. DC-SIGN (CD209) mediates dengue virus infection of human dendritic cells. J Exp Med. 2003;197:823-9 pubmed
    ..Viruses produced by dendritic cells are infectious for DC-SIGN- and L-SIGN-bearing THP-1 cells and other permissive cell lines. Therefore, DC-SIGN may be considered as a new target for designing therapies that block dengue infection. ..
  8. Pryor M, Azzola L, Wright P, Davidson A. Histidine 39 in the dengue virus type 2 M protein has an important role in virus assembly. J Gen Virol. 2004;85:3627-36 pubmed
    ..The results of this study pinpoint a critical residue in the M protein that potentially plays a role in viral morphogenesis, secretion and entry. ..
  9. Bartelma G, Padmanabhan R. Expression, purification, and characterization of the RNA 5'-triphosphatase activity of dengue virus type 2 nonstructural protein 3. Virology. 2002;299:122-32 pubmed
    ..Biochemical and mutational analyses of the NS3 protein indicate that the nucleoside triphosphatase and 5'-RNA triphosphatase activities of NS3 share a common active site. ..
  10. Egloff M, Benarroch D, Selisko B, Romette J, Canard B. An RNA cap (nucleoside-2'-O-)-methyltransferase in the flavivirus RNA polymerase NS5: crystal structure and functional characterization. EMBO J. 2002;21:2757-68 pubmed
    ..As RNA capping is an essential viral function, these results provide a structural basis for the rational design of drugs against the emerging flaviviruses. ..
  11. Johansson M, Brooks A, Jans D, Vasudevan S. A small region of the dengue virus-encoded RNA-dependent RNA polymerase, NS5, confers interaction with both the nuclear transport receptor importin-beta and the viral helicase, NS3. J Gen Virol. 2001;82:735-45 pubmed
    ..The direct interaction of importin-beta with NS5 has implications for the mechanism by which this normally cytoplasmic protein may be targetted to the nucleus. ..
  12. Selisko B, Dutartre H, Guillemot J, Debarnot C, Benarroch D, Khromykh A, et al. Comparative mechanistic studies of de novo RNA synthesis by flavivirus RNA-dependent RNA polymerases. Virology. 2006;351:145-58 pubmed publisher
    ..This suggests that they display a higher conformational flexibility upon the transition from initiation to elongation...
  13. Puttikhunt C, Kasinrerk W, Srisa ad S, Duangchinda T, Silakate W, Moonsom S, et al. Production of anti-dengue NS1 monoclonal antibodies by DNA immunization. J Virol Methods. 2003;109:55-61 pubmed
    ..This has opened up a possibility of producing monoclonal antibodies to rare viral proteins that are difficult to isolate or purify...
  14. Leitmeyer K, Vaughn D, Watts D, Salas R, Villalobos I, de Chacon -, et al. Dengue virus structural differences that correlate with pathogenesis. J Virol. 1999;73:4738-47 pubmed
    ..This new approach to the study of dengue virus genome differences should better reflect the true composition of viral RNA populations in the natural host and permit their association with pathogenesis. ..
  15. Nomaguchi M, Ackermann M, Yon C, You S, Padmanabhan R, Padmanbhan R. De novo synthesis of negative-strand RNA by Dengue virus RNA-dependent RNA polymerase in vitro: nucleotide, primer, and template parameters. J Virol. 2003;77:8831-42 pubmed
  16. Modis Y, Ogata S, Clements D, Harrison S. Structure of the dengue virus envelope protein after membrane fusion. Nature. 2004;427:313-9 pubmed
    ..Specific features of the folded-back structure suggest strategies for inhibiting flavivirus entry. ..
  17. Kuhn R, Zhang W, Rossmann M, Pletnev S, Corver J, Lenches E, et al. Structure of dengue virus: implications for flavivirus organization, maturation, and fusion. Cell. 2002;108:717-25 pubmed
    ..The structure suggests that flaviviruses, and by analogy also alphaviruses, employ a fusion mechanism in which the distal beta barrels of domain II of the glycoprotein E are inserted into the cellular membrane. ..
  18. MacKenzie J, Jones M, Young P. Immunolocalization of the dengue virus nonstructural glycoprotein NS1 suggests a role in viral RNA replication. Virology. 1996;220:232-40 pubmed publisher
    ..These findings provide further insights into the maturation pathway of NS1 and suggest a possible role for this protein in viral RNA replication...
  19. Ackermann M, Padmanabhan R. De novo synthesis of RNA by the dengue virus RNA-dependent RNA polymerase exhibits temperature dependence at the initiation but not elongation phase. J Biol Chem. 2001;276:39926-37 pubmed
    ..A model is proposed that a specific conformation of the viral polymerase and/or structure at the 3' end of the template RNA is required for de novo initiation. ..
  20. Zhang W, Chipman P, Corver J, Johnson P, Zhang Y, Mukhopadhyay S, et al. Visualization of membrane protein domains by cryo-electron microscopy of dengue virus. Nat Struct Biol. 2003;10:907-12 pubmed
    ..This is one of only a few determinations of the disposition of transmembrane proteins in situ and shows that the nucleocapsid core and envelope proteins do not have a direct interaction in the mature virus. ..
  21. Westaway E, Khromykh A, Kenney M, MacKenzie J, Jones M. Proteins C and NS4B of the flavivirus Kunjin translocate independently into the nucleus. Virology. 1997;234:31-41 pubmed publisher
    ..Dual IF with antibodies to double-stranded RNA showed that cytoplasmic locations of C and NS4B were apparently associated in part with the sites of viral RNA synthesis which were resistant to solubilization by Triton X-100...
  22. Kinney R, Butrapet S, Chang G, Tsuchiya K, Roehrig J, Bhamarapravati N, et al. Construction of infectious cDNA clones for dengue 2 virus: strain 16681 and its attenuated vaccine derivative, strain PDK-53. Virology. 1997;230:300-8 pubmed
    ..Although the NS3-250-Val mutation clearly affected virus replication in vitro, it was not a major determinant of attenuation for PDK-53 virus in suckling mice. ..
  23. Alcon LePoder S, Drouet M, Roux P, Frenkiel M, Arborio M, Durand Schneider A, et al. The secreted form of dengue virus nonstructural protein NS1 is endocytosed by hepatocytes and accumulates in late endosomes: implications for viral infectivity. J Virol. 2005;79:11403-11 pubmed publisher
  24. Schlesinger J, Brandriss M, Walsh E. Protection of mice against dengue 2 virus encephalitis by immunization with the dengue 2 virus non-structural glycoprotein NS1. J Gen Virol. 1987;68 ( Pt 3):853-7 pubmed
    ..Induction of a protective immune response by NS1 suggests that it be considered for incorporation into possible synthetic or recombinant DNA DEN vaccines. ..
  25. Chung K, Liszewski M, Nybakken G, Davis A, Townsend R, Fremont D, et al. West Nile virus nonstructural protein NS1 inhibits complement activation by binding the regulatory protein factor H. Proc Natl Acad Sci U S A. 2006;103:19111-6 pubmed publisher
    ..Accordingly, extracellular NS1 may function to minimize immune system targeting of West Nile virus by decreasing complement recognition of infected cells...
  26. Flamand M, Megret F, Mathieu M, Lepault J, Rey F, Deubel V. Dengue virus type 1 nonstructural glycoprotein NS1 is secreted from mammalian cells as a soluble hexamer in a glycosylation-dependent fashion. J Virol. 1999;73:6104-10 pubmed
    ..These results, together with observations related to the absence of secretion of NS1 from Den-infected insect cells, suggest that maturation and secretion of hexameric NS1 depend on the glycosylation status of the host cell...
  27. Hung S, Lee P, Chen H, Chen L, Kao C, King C. Analysis of the steps involved in Dengue virus entry into host cells. Virology. 1999;257:156-67 pubmed
    ..This suggests that cell surface heparan sulfate functions in both viral attachment and penetration of DEN-2 virus. In conclusion, our results further elucidated some aspects of the dengue virus entry process. ..
  28. Yu I, Zhang W, Holdaway H, Li L, Kostyuchenko V, Chipman P, et al. Structure of the immature dengue virus at low pH primes proteolytic maturation. Science. 2008;319:1834-7 pubmed publisher
    ..These results suggest a mechanism by which flaviviruses are processed and stabilized in the host cell secretory pathway. ..
  29. Mercado Curiel R, Esquinca Avil s H, Tovar R, D az Badillo A, Camacho Nuez M. The four serotypes of dengue recognize the same putative receptors in Aedes aegypti midgut and Ae. albopictus cells. BMC Microbiol. 2006;6:85 pubmed publisher
    ..aegypti midgut. Our results strongly suggest that R67 and R80 are receptors for the four serotypes of dengue virus in the midgut cells of Ae. aegypti and in C6/36 Ae. albopictus cells...
  30. Alvarez D, Lodeiro M, Ludue a S, Pietrasanta L, Gamarnik A. Long-range RNA-RNA interactions circularize the dengue virus genome. J Virol. 2005;79:6631-43 pubmed publisher
    ..Since sequence complementarity between the ends of the genome is required for dengue virus viability, we propose that cyclization of the RNA is a required conformation for viral replication...
  31. Chen M, Lin C, Lei H, Lin S, Liu H, Yeh T, et al. Deletion of the C-terminal region of dengue virus nonstructural protein 1 (NS1) abolishes anti-NS1-mediated platelet dysfunction and bleeding tendency. J Immunol. 2009;183:1797-803 pubmed publisher
    ..These findings may be important not only for understanding dengue hemorrhagic disease pathogenesis but also for dengue vaccine development...
  32. Bera A, Kuhn R, Smith J. Functional characterization of cis and trans activity of the Flavivirus NS2B-NS3 protease. J Biol Chem. 2007;282:12883-92 pubmed publisher
    ..Formation of an active protease was found to require neither cleavage of NS2B from NS3 nor a free NS3 N terminus. Evidence was also obtained for product inhibition of the protease by the cleaved C terminus of NS2B...
  33. Diwaker D, Mishra K, Ganju L, Singh S. Protein disulfide isomerase mediates dengue virus entry in association with lipid rafts. Viral Immunol. 2015;28:153-60 pubmed publisher
    ..Disruption of this key interaction between PDI and NS1 could be an important therapeutic strategy to block DENV infection. ..
  34. Folly B, Weffort Santos A, Fathman C, Soares L. Dengue-2 structural proteins associate with human proteins to produce a coagulation and innate immune response biased interactome. BMC Infect Dis. 2011;11:34 pubmed publisher
  35. Shyu H, Lin Y, Chen L, Wang Y, Yeh T, Su S, et al. The dengue virus envelope protein induced PAI-1 gene expression via MEK/ERK pathways. Thromb Haemost. 2010;104:1219-27 pubmed publisher
    ..The results suggest that the MEK/ERK signalling pathways mediate the EIII-dependent induction of PAI-1 gene expression via the proximal promoter region. ..
  36. Lindenbach B, Rice C. Genetic interaction of flavivirus nonstructural proteins NS1 and NS4A as a determinant of replicase function. J Virol. 1999;73:4611-21 pubmed
    ..These findings suggest a potential mechanism for integrating NS1 into the cytoplasmic process of RNA replication...
  37. Gebhard L, Incicco J, Smal C, Gallo M, Gamarnik A, Kaufman S. Monomeric nature of dengue virus NS3 helicase and thermodynamic analysis of the interaction with single-stranded RNA. Nucleic Acids Res. 2014;42:11668-86 pubmed publisher
    ..We found that binding of NS3h to ssRNA oligonucleotides and to poly(A) is characterized by minimum and occluded binding site sizes both of 10 nucleotides and by a weak positive cooperativity between adjacent proteins. ..
  38. Cleaves G, Ryan T, Schlesinger R. Identification and characterization of type 2 dengue virus replicative intermediate and replicative form RNAs. Virology. 1981;111:73-83 pubmed
  39. Junjhon J, Edwards T, Utaipat U, Bowman V, Holdaway H, Zhang W, et al. Influence of pr-M cleavage on the heterogeneity of extracellular dengue virus particles. J Virol. 2010;84:8353-8 pubmed publisher
    ..These findings are consistent with a model suggesting the progressive mode of prM cleavage...
  40. Alvarez D, Lodeiro M, Filomatori C, Fucito S, Mondotte J, Gamarnik A. Structural and functional analysis of dengue virus RNA. Novartis Found Symp. 2006;277:120-32; discussion 132-5, 251-3 pubmed
    ..Furthermore, a systematic mutational analysis of UAR sequences indicated that, beside the role in RNA cyclization, specific nucleotides within UAR are also important for efficient RNA synthesis...
  41. Mu oz Jord n J, Laurent Rolle M, Ashour J, Mart nez Sobrido L, Ashok M, Lipkin W, et al. Inhibition of alpha/beta interferon signaling by the NS4B protein of flaviviruses. J Virol. 2005;79:8004-13 pubmed publisher
  42. Clum S, Ebner K, Padmanabhan R. Cotranslational membrane insertion of the serine proteinase precursor NS2B-NS3(Pro) of dengue virus type 2 is required for efficient in vitro processing and is mediated through the hydrophobic regions of NS2B. J Biol Chem. 1997;272:30715-23 pubmed
    ..Deletion of hydrophobic regions of NS2B, leaving only the conserved hydrophilic domain of 40 amino acids, resulted in highly efficient processing of the 2B-3 site in vitro in the absence of microsomal membranes...
  43. Gaines P, Olson K, Higgs S, Powers A, Beaty B, Blair C. Pathogen-derived resistance to dengue type 2 virus in mosquito cells by expression of the premembrane coding region of the viral genome. J Virol. 1996;70:2132-7 pubmed
    ..Cells expressing prM protein demonstrated some breakthrough of DEN-2 virus when challenged at an MOI of 10. However, expressed untranslatable sense prM RNA conferred complete protection to challenge at the high MOI...
  44. Huerta V, Chinea G, Fleitas N, Sarr a M, S nchez J, Toledo P, et al. Characterization of the interaction of domain III of the envelope protein of dengue virus with putative receptors from CHO cells. Virus Res. 2008;137:225-34 pubmed publisher
  45. Hahn Y, Galler R, Hunkapiller T, Dalrymple J, Strauss J, Strauss E. Nucleotide sequence of dengue 2 RNA and comparison of the encoded proteins with those of other flaviviruses. Virology. 1988;162:167-80 pubmed
  46. Ren J, Ding T, Zhang W, Song J, Ma W. Does Japanese encephalitis virus share the same cellular receptor with other mosquito-borne flaviviruses on the C6/36 mosquito cells?. Virol J. 2007;4:83 pubmed publisher
  47. Patkar C, Kuhn R. Development of novel antivirals against flaviviruses. Novartis Found Symp. 2006;277:41-52; discussion 52-6, 71-3, 251-3 pubmed
  48. Deubel V, Kinney R, Trent D. Nucleotide sequence and deduced amino acid sequence of the nonstructural proteins of dengue type 2 virus, Jamaica genotype: comparative analysis of the full-length genome. Virology. 1988;165:234-44 pubmed
    ..Proteins NS1, NS3, and NS5 are the most conserved. Conserved amino acid stretches present in all flavivirus proteins may be involved in common essential biological functions...
  49. Henchal E, Henchal L, Schlesinger J. Synergistic interactions of anti-NS1 monoclonal antibodies protect passively immunized mice from lethal challenge with dengue 2 virus. J Gen Virol. 1988;69 ( Pt 8):2101-7 pubmed publisher
    ..These results may affect the design of recombinant dengue vaccines which may require the inclusion of serotype-specific antigenic domains...
  50. Zou J, Lee L, Wang Q, Xie X, Lu S, Yau Y, et al. Mapping the Interactions between the NS4B and NS3 proteins of dengue virus. J Virol. 2015;89:3471-83 pubmed publisher
    ..In addition, this study has established the rationale and assays to search for inhibitors disrupting the NS3-NS4B interaction for antiviral drug discovery. ..
  51. Wong S, Haqshenas G, Gowans E, Mackenzie J. The dengue virus M protein localises to the endoplasmic reticulum and forms oligomers. FEBS Lett. 2012;586:1032-7 pubmed publisher
    ..In addition, cross-linking studies showed that M can form dimers and tetramers. These findings suggest that M behaves as a secretory protein analogous to the major envelope protein E. ..
  52. Gil L, Bernardo L, Pav n A, Izquierdo A, Vald s I, Lazo L, et al. Recombinant nucleocapsid-like particles from dengue-2 induce functional serotype-specific cell-mediated immunity in mice. J Gen Virol. 2012;93:1204-14 pubmed publisher
    ..Further studies in non-human primates or humanized mice should be carried out to elucidate the usefulness of the NLPs as a potential vaccine candidate against dengue disease...
  53. Livingston P, Kurane I, Dai L, Okamoto Y, Lai C, Men R, et al. Dengue virus-specific, HLA-B35-restricted, human CD8+ cytotoxic T lymphocyte (CTL) clones. Recognition of NS3 amino acids 500 to 508 by CTL clones of two different serotype specificities. J Immunol. 1995;154:1287-95 pubmed
    ..These results indicate that CD8+ CTL clones that use different TCR and demonstrate two distinct serotype specificities recognize the same 9-mer peptide in the context of HLA-B35...
  54. Winkler G, Maxwell S, Ruemmler C, Stollar V. Newly synthesized dengue-2 virus nonstructural protein NS1 is a soluble protein but becomes partially hydrophobic and membrane-associated after dimerization. Virology. 1989;171:302-5 pubmed
    ..In experiments in which infected cells were treated with tunicamycin it was shown that the glycosylation of NS1 was not required for either the dimerization or the membrane association...
  55. Lisova O, Hardy F, Petit V, Bedouelle H. Mapping to completeness and transplantation of a group-specific, discontinuous, neutralizing epitope in the envelope protein of dengue virus. J Gen Virol. 2007;88:2387-97 pubmed publisher
    ..The epitope straddles residues of ED3 that are involved in virulence, e.g. Asn/Asp390. These results define the epitope of mAb4E11 as an antigenic signature of the DENV group and suggest mechanisms for its neutralization potency...
  56. Hsieh S, Liu I, King C, Chang G, Wang W. A strong endoplasmic reticulum retention signal in the stem-anchor region of envelope glycoprotein of dengue virus type 2 affects the production of virus-like particles. Virology. 2008;374:338-50 pubmed publisher
    ..Moreover, co-expression of C protein can enhance the production of DENV2 VLPs, suggesting a mechanism of facilitating viral particle formation during DENV2 replication...
  57. Deubel V, Bordier M, Megret F, Gentry M, Schlesinger J, Girard M. Processing, secretion, and immunoreactivity of carboxy terminally truncated dengue-2 virus envelope proteins expressed in insect cells by recombinant baculoviruses. Virology. 1991;180:442-7 pubmed
    ..The type-specific neutralizing epitopes were conserved in the recombinant proteins as shown with a panel of monoclonal antibodies. ..
  58. Chiu M, Shih H, Yang T, Yang Y. The type 2 dengue virus envelope protein interacts with small ubiquitin-like modifier-1 (SUMO-1) conjugating enzyme 9 (Ubc9). J Biomed Sci. 2007;14:429-44 pubmed publisher
    ..This is the first report that DV envelope proteins can interact with the protein of sumoylation system and Ubc9 may involve in the host defense system to prevent virus propagation...
  59. Garc a Montalvo B, Medina F, Del Angel R. La protein binds to NS5 and NS3 and to the 5' and 3' ends of Dengue 4 virus RNA. Virus Res. 2004;102:141-50 pubmed publisher
    ..Moreover, these proteins also interact with the nonstructural proteins NS5 and NS3. The role of the NS5-La and NS3-La interaction in U937 cells remains to be established...
  60. Lin C, Lei H, Shiau A, Liu H, Yeh T, Chen S, et al. Endothelial cell apoptosis induced by antibodies against dengue virus nonstructural protein 1 via production of nitric oxide. J Immunol. 2002;169:657-64 pubmed
    ..Endothelial cell damage may cause vascular leakage that contributes to the pathogenesis of dengue disease...
  61. Avirutnan P, Fuchs A, Hauhart R, Somnuke P, Youn S, Diamond M, et al. Antagonism of the complement component C4 by flavivirus nonstructural protein NS1. J Exp Med. 2010;207:793-806 pubmed publisher
    ..Through this mechanism, NS1 protects DENV from complement-dependent neutralization in solution. These studies define a novel immune evasion mechanism for restricting complement control of microbial infection...
  62. Filomatori C, Lodeiro M, Alvarez D, Samsa M, Pietrasanta L, Gamarnik A. A 5' RNA element promotes dengue virus RNA synthesis on a circular genome. Genes Dev. 2006;20:2238-49 pubmed publisher
    ..These findings provide an explanation for the strict requirement of dengue virus genome cyclization during viral replication...
  63. Clyde K, Harris E. RNA secondary structure in the coding region of dengue virus type 2 directs translation start codon selection and is required for viral replication. J Virol. 2006;80:2170-82 pubmed publisher
    ..While numerous regulatory elements have been identified in the untranslated regions of RNA viral genomes, we show that the cHP is a coding-region RNA element that directs start codon selection and is required for viral replication...
  64. Chua J, Bhuvanakantham R, Chow V, Ng M. Recombinant non-structural 1 (NS1) protein of dengue-2 virus interacts with human STAT3beta protein. Virus Res. 2005;112:85-94 pubmed publisher
    ..Since the STAT3beta protein is an acute-phase response factor, its interaction with NS1 protein may influence the pathological changes observed in dengue fever, dengue hemorrhagic fever and dengue shock syndrome...
  65. Leung D, Schroder K, White H, Fang N, Stoermer M, Abbenante G, et al. Activity of recombinant dengue 2 virus NS3 protease in the presence of a truncated NS2B co-factor, small peptide substrates, and inhibitors. J Biol Chem. 2001;276:45762-71 pubmed publisher
    ..Aprotinin was the only standard serine protease inhibitor to be active, whereas a number of peptide substrate analogues were found to be competitive inhibitors at micromolar concentrations...
  66. Falconar A, Martinez F. The NS1 glycoprotein can generate dramatic antibody-enhanced dengue viral replication in normal out-bred mice resulting in lethal multi-organ disease. PLoS ONE. 2011;6:e21024 pubmed publisher
    ..The model provides potential for assessing DENV strain pathogenicity and anti-DENV therapies in normal mice. ..
  67. Young P, Hilditch P, Bletchly C, Halloran W. An antigen capture enzyme-linked immunosorbent assay reveals high levels of the dengue virus protein NS1 in the sera of infected patients. J Clin Microbiol. 2000;38:1053-7 pubmed
  68. Pryor M, Wright P. The effects of site-directed mutagenesis on the dimerization and secretion of the NS1 protein specified by dengue virus. Virology. 1993;194:769-80 pubmed publisher
    ..Only the proteins which formed dimers were detected at the cell surface and in the extracellular medium. No monomers were secreted...
  69. Li L, Lok S, Yu I, Zhang Y, Kuhn R, Chen J, et al. The flavivirus precursor membrane-envelope protein complex: structure and maturation. Science. 2008;319:1830-4 pubmed publisher
    ..The structure provides a basis for identifying the stages of its pH-directed conformational metamorphosis during maturation, ending with release of pr when budding from the host...
  70. Chatel Chaix L, Fischl W, Scaturro P, Cortese M, Kallis S, Bartenschlager M, et al. A Combined Genetic-Proteomic Approach Identifies Residues within Dengue Virus NS4B Critical for Interaction with NS3 and Viral Replication. J Virol. 2015;89:7170-86 pubmed publisher
    ..The strong correlation between NS3-NS4B interaction and RNA replication provides strong evidence that this complex plays a pivotal role in the viral replication cycle, hence representing a promising antiviral drug target. ..
  71. Bulich R, Aaskov J. Nuclear localization of dengue 2 virus core protein detected with monoclonal antibodies. J Gen Virol. 1992;73 ( Pt 11):2999-3003 pubmed publisher
  72. Johnson A, Guirakhoo F, Roehrig J. The envelope glycoproteins of dengue 1 and dengue 2 viruses grown in mosquito cells differ in their utilization of potential glycosylation sites. Virology. 1994;203:241-9 pubmed publisher
    ..These DEN virus serotypes are thus heterogeneous in their use of glycosylation sites. We also determined by a lectin-binding assay that the attached carbohydrates for both viruses were likely to be of the high-mannose type...
  73. Khumthong R, Niyomrattanakit P, Chanprapaph S, Angsuthanasombat C, Panyim S, Katzenmeier G. Steady-state cleavage kinetics for dengue virus type 2 ns2b-ns3(pro) serine protease with synthetic peptides. Protein Pept Lett. 2003;10:19-26 pubmed
    ..A marked difference in cleavage efficiency was found for the NS2B/NS3 substrate and the remaining 3 peptides based on the NS2A/NS2B, NS3/NS4A and NS4A/NS5 cleavage sites. ..
  74. Erb S, Butrapet S, Moss K, Luy B, Childers T, Calvert A, et al. Domain-III FG loop of the dengue virus type 2 envelope protein is important for infection of mammalian cells and Aedes aegypti mosquitoes. Virology. 2010;406:328-35 pubmed publisher
    ..Reduced binding of DENV2 type-specific monoclonal antibody 3H5 to mutant viruses confirmed the FG loop motif as its target epitope...
  75. Valle R, Falgout B. Mutagenesis of the NS3 protease of dengue virus type 2. J Virol. 1998;72:624-32 pubmed
    ..Mutations that decrease protease activity without abolishing it are candidates for introduction into the dengue virus infectious full-length cDNA clone with the aim of creating potentially attenuated virus stocks...
  76. Chatel Chaix L, Cortese M, Romero Brey I, Bender S, Neufeldt C, Fischl W, et al. Dengue Virus Perturbs Mitochondrial Morphodynamics to Dampen Innate Immune Responses. Cell Host Microbe. 2016;20:342-356 pubmed publisher
    ..As Zika virus infection induces similar mitochondria elongation, this perturbation may protect DENV and related viruses from innate immunity and create a favorable replicative environment. ..