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Science 29 January 1988:
Vol. 239. no. 4839, pp. 476 - 481
DOI: 10.1126/science.3277268
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Articles

Science, Vol 239, Issue 4839, 476-481
Copyright © 1988 by American Association for the Advancement of Science

articles

Pathogenesis of dengue: challenges to molecular biology

SB Halstead

Division of Health Sciences, Rockefeller Foundation, New York, NY 10036.

Dengue viruses occur as four antigenically related but distinct serotypes transmitted to humans by Aedes aegypti mosquitoes. 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. This severe syndrome, which recently has also been identified in children infected with the virus in Puerto Rico, is characterized by increased vascular permeability and abnormal hemostasis. It occurs in infants less than 1 year of age born to dengue-immune mothers and in children 1 year and older who are immune to one serotype of dengue virus and are experiencing infection with a second serotype. Dengue viruses replicate in cells of mononuclear phagocyte lineage, and subneutralizing concentrations of dengue antibody enhance dengue virus infection in these cells. This antibody-dependent enhancement of infection regulates dengue disease in human beings, although disease severity may also be controlled genetically, possibly by permitting and restricting the growth of virus in monocytes. Monoclonal antibodies show heterogeneous distribution of antigenic epitopes on dengue viruses. These epitopes serve to regulate disease: when antibodies to shared antigens partially neutralize heterotypic virus, infection and disease are dampened; enhancing antibodies alone result in heightened disease response. Further knowledge of the structure of dengue genomes should permit rapid advances in understanding the pathogenetic mechanisms of dengue.


THIS ARTICLE HAS BEEN CITED BY OTHER ARTICLES:
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Generation and Characterization of Monoclonal Antibodies against Dengue Virus Type 1 for Epitope Mapping and Serological Detection by Epitope-Based Peptide Antigens.
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Domain III from class II fusion proteins functions as a dominant-negative inhibitor of virus membrane fusion.
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J. Virol. 79, 7291-7299
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S. Matheus, X. Deparis, B. Labeau, J. Lelarge, J. Morvan, and P. Dussart (2005)
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J. Virol. 79, 5516-5528
   Abstract »    Full Text »    PDF »
Inhibition of Dengue Virus Serotypes 1 to 4 in Vero Cell Cultures with Morpholino Oligomers.
R. M. Kinney, C. Y.-H. Huang, B. C. Rose, A. D. Kroeker, T. W. Dreher, P. L. Iversen, and D. A. Stein (2005)
J. Virol. 79, 5116-5128
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Evasion of antibody neutralization in emerging severe acute respiratory syndrome coronaviruses.
Z.-y. Yang, H. C. Werner, W.-p. Kong, K. Leung, E. Traggiai, A. Lanzavecchia, and G. J. Nabel (2005)
PNAS 102, 797-801
   Abstract »    Full Text »    PDF »
Variable Surface Epitopes in the Crystal Structure of Dengue Virus Type 3 Envelope Glycoprotein.
Y. Modis, S. Ogata, D. Clements, and S. C. Harrison (2005)
J. Virol. 79, 1223-1231
   Abstract »    Full Text »    PDF »
Identification of Residues in the Dengue Virus Type 2 NS2B Cofactor That Are Critical for NS3 Protease Activation.
P. Niyomrattanakit, P. Winoyanuwattikun, S. Chanprapaph, C. Angsuthanasombat, S. Panyim, and G. Katzenmeier (2004)
J. Virol. 78, 13708-13716
   Abstract »    Full Text »    PDF »
Localization and Characterization of Flavivirus Envelope Glycoprotein Cross-Reactive Epitopes.
W. D. Crill and G.-J. J. Chang (2004)
J. Virol. 78, 13975-13986
   Abstract »    Full Text »    PDF »
Chimpanzee Fab Fragments and a Derived Humanized Immunoglobulin G1 Antibody That Efficiently Cross-Neutralize Dengue Type 1 and Type 2 Viruses.
A. P. Goncalvez, R. Men, C. Wernly, R. H. Purcell, and C.-J. Lai (2004)
J. Virol. 78, 12910-12918
   Abstract »    Full Text »    PDF »
GENETICALLY MODIFIED, LIVE ATTENUATED DENGUE VIRUS TYPE 3 VACCINE CANDIDATES.
J. E. BLANEY JR., C. T. HANSON, C.-Y. FIRESTONE, K. A. HANLEY, B. R. MURPHY, and S. S. WHITEHEAD (2004)
Am J Trop Med Hyg 71, 811-821
   Abstract »    Full Text »    PDF »
Study of Sequence Variation of Dengue Type 3 Virus in Naturally Infected Mosquitoes and Human Hosts: Implications for Transmission and Evolution.
S.-R. Lin, S.-C. Hsieh, Y.-Y. Yueh, T.-H. Lin, D.-Y. Chao, W.-J. Chen, C.-C. King, and W.-K. Wang (2004)
J. Virol. 78, 12717-12721
   Abstract »    Full Text »    PDF »
OXIDATIVE STRESS IN ADULT DENGUE PATIENTS.
L. GIL, G. MARTINEZ, R. TAPANES, O. CASTRO, D. GONZALEZ, L. BERNARDO, S. VAZQUEZ, G. KOURI, and M. G. GUZMAN (2004)
Am J Trop Med Hyg 71, 652-657
   Abstract »    Full Text »    PDF »
Dengue viral infections.
G N Malavige, S Fernando, D J Fernando, and S L Seneviratne (2004)
Postgrad. Med. J. 80, 588-601
   Abstract »    Full Text »    PDF »
A Single Amino Acid Substitution in the Envelope Protein of Chimeric Yellow Fever-Dengue 1 Vaccine Virus Reduces Neurovirulence for Suckling Mice and Viremia/Viscerotropism for Monkeys.
F. Guirakhoo, Z. Zhang, G. Myers, B. W. Johnson, K. Pugachev, R. Nichols, N. Brown, I. Levenbook, K. Draper, S. Cyrek, et al. (2004)
J. Virol. 78, 9998-10008
   Abstract »    Full Text »    PDF »
ANALYSIS OF RECOMBINANT DENGUE VIRUS POLYPEPTIDES FOR DENGUE DIAGNOSIS AND EVALUATION OF THE HUMORAL IMMUNE RESPONSE.
F. B. D. SANTOS, M. P. MIAGOSTOVICH, R. M. R. NOGUEIRA, H. G. SCHATZMAYR, L. W. RILEY, and E. HARRIS (2004)
Am J Trop Med Hyg 71, 144-152
   Abstract »    Full Text »    PDF »
Flavivirus Encephalitis.
T. Solomon (2004)
N. Engl. J. Med. 351, 370-378
   Full Text »    PDF »
Current Advances in Dengue Diagnosis.
P.-Y. Shu and J.-H. Huang (2004)
Clin. Vaccine Immunol. 11, 642-650
   Full Text »
Dengue Virus Serotyping Based on Envelope and Membrane and Nonstructural Protein NS1 Serotype-Specific Capture Immunoglobulin M Enzyme-Linked Immunosorbent Assays.
P.-Y. Shu, L.-K. Chen, S.-F. Chang, C.-L. Su, L.-J. Chien, C. Chin, T.-H. Lin, and J.-H. Huang (2004)
J. Clin. Microbiol. 42, 2489-2494
   Abstract »    Full Text »    PDF »
Determination of the Disulfide Bond Arrangement of Dengue Virus NS1 Protein.
T. P. Wallis, C.-Y. Huang, S. B. Nimkar, P. R. Young, and J. J. Gorman (2004)
J. Biol. Chem. 279, 20729-20741
   Abstract »    Full Text »    PDF »
Safety and Efficacy of Chimeric Yellow Fever-Dengue Virus Tetravalent Vaccine Formulations in Nonhuman Primates.
F. Guirakhoo, K. Pugachev, Z. Zhang, G. Myers, I. Levenbook, K. Draper, J. Lang, S. Ocran, F. Mitchell, M. Parsons, et al. (2004)
J. Virol. 78, 4761-4775
   Abstract »    Full Text »    PDF »
Use of an Immunoglobulin G Avidity Test To Discriminate between Primary and Secondary Dengue Virus Infections.
V. A. U. F. de Souza, S. Fernandes, E. S. Araujo, A. F. Tateno, O. M. N. P. F. Oliveira, R. d. R. Oliveira, and C. S. Pannuti (2004)
J. Clin. Microbiol. 42, 1782-1784
   Abstract »    Full Text »    PDF »
Interferon-Dependent Immunity Is Essential for Resistance to Primary Dengue Virus Infection in Mice, Whereas T- and B-Cell-Dependent Immunity Are Less Critical.
S. Shresta, J. L. Kyle, H. M. Snider, M. Basavapatna, P. R. Beatty, and E. Harris (2004)
J. Virol. 78, 2701-2710
   Abstract »    Full Text »    PDF »
Norovirus Capture with Histo-Blood Group Antigens Reveals Novel Virus-Ligand Interactions.
P. R. Harrington, J. Vinje, C. L. Moe, and R. S. Baric (2004)
J. Virol. 78, 3035-3045
   Abstract »    Full Text »    PDF »
RISK FACTORS FOR INFECTION DURING A SEVERE DENGUE OUTBREAK IN EL SALVADOR IN 2000.
J. M. HAYES, E. GARCIA-RIVERA, R. FLORES-REYNA, G. SUAREZ-RANGEL, T. RODRIGUEZ-MATA, R. COTO-PORTILLO, R. BALTRONS-ORELLANA, E. MENDOZA-RODRIGUEZ, B. FUENTES DE GARAY, J. JUBIS-ESTRADA, et al. (2003)
Am J Trop Med Hyg 69, 629-633
   Abstract »    Full Text »    PDF »
Dengue 2 PDK-53 Virus as a Chimeric Carrier for Tetravalent Dengue Vaccine Development.
C. Y.-H. Huang, S. Butrapet, K. R. Tsuchiya, N. Bhamarapravati, D. J. Gubler, and R. M. Kinney (2003)
J. Virol. 77, 11436-11447
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Identification of a dengue virus type 2 (DEN-2) serotype-specific B-cell epitope and detection of DEN-2-immunized animal serum samples using an epitope-based peptide antigen.
H.-C. Wu, M.-Y. Jung, C.-Y. Chiu, T.-T. Chao, S.-C. Lai, J.-T. Jan, and M.-F. Shaio (2003)
J. Gen. Virol. 84, 2771-2779
   Abstract »    Full Text »    PDF »
Selection-Driven Evolution of Emergent Dengue Virus.
S. N. Bennett, E. C. Holmes, M. Chirivella, D. M. Rodriguez, M. Beltran, V. Vorndam, D. J. Gubler, and W. O. McMillan (2003)
Mol. Biol. Evol. 20, 1650-1658
   Abstract »    Full Text »    PDF »
Antibody-dependent enhancement of Murray Valley encephalitis virus virulence in mice.
M. J. Wallace, D. W. Smith, A. K. Broom, J. S. Mackenzie, R. A. Hall, G. R. Shellam, and P. C. McMinn (2003)
J. Gen. Virol. 84, 1723-1728
   Abstract »    Full Text »    PDF »
ALTERATION OF CLINICAL OUTCOME AND HISTOPATHOLOGY OF YELLOW FEVER VIRUS INFECTION IN A HAMSTER MODEL BY PREVIOUS INFECTION WITH HETEROLOGOUS FLAVIVIRUSES.
S.-Y. XIAO, H. GUZMAN, A. P. A. T. DA ROSA, H.-B. ZHU, and R. B. TESH (2003)
Am J Trop Med Hyg 68, 695-703
   Abstract »    Full Text »    PDF »
Public versus personal serotypes of a viral quasispecies.
L. Hunziker, A. Ciurea, M. Recher, H. Hengartner, and R. M. Zinkernagel (2003)
PNAS 100, 6015-6020
   Abstract »    Full Text »    PDF »
A Japanese Encephalitis Virus Peptide Present on Johnson Grass Mosaic Virus-Like Particles Induces Virus-Neutralizing Antibodies and Protects Mice against Lethal Challenge.
M. Saini and S. Vrati (2003)
J. Virol. 77, 3487-3494
   Abstract »    Full Text »    PDF »
INCREASED APOPTOSIS AND EXPRESSION OF TUMOR NECROSIS FACTOR-{alpha} CAUSED BY INFECTION OF CULTURED HUMAN MONOCYTES WITH DENGUE VIRUS.
L. M. ESPINA, N. J. VALERO, J. M. HERNANDEZ, and J. A. MOSQUERA (2003)
Am J Trop Med Hyg 68, 48-53
   Abstract »    Full Text »    PDF »
Inferring the Rate and Time-Scale of Dengue Virus Evolution.
S. S. Twiddy, E. C. Holmes, and A. Rambaut (2003)
Mol. Biol. Evol. 20, 122-129
   Abstract »    Full Text »    PDF »
Detection of Dengue Virus Replication in Peripheral Blood Mononuclear Cells from Dengue Virus Type 2-Infected Patients by a Reverse Transcription-Real-Time PCR Assay.
W.-K. Wang, T.-L. Sung, Y.-C. Tsai, C.-L. Kao, S.-M. Chang, and C.-C. King (2002)
J. Clin. Microbiol. 40, 4472-4478
   Abstract »    Full Text »    PDF »
Serological Differentiation of Infections with Dengue Virus Serotypes 1 to 4 by Using Recombinant Antigens.
D. Ludolfs, S. Schilling, J. Altenschmidt, and H. Schmitz (2002)
J. Clin. Microbiol. 40, 4317-4320
   Abstract »    Full Text »    PDF »
The Interdomain Region of Dengue NS5 Protein That Binds to the Viral Helicase NS3 Contains Independently Functional Importin beta 1 and Importin alpha /beta -Recognized Nuclear Localization Signals.
A. J. Brooks, M. Johansson, A. V. John, Y. Xu, D. A. Jans, and S. G. Vasudevan (2002)
J. Biol. Chem. 277, 36399-36407
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Activation of Terminally Differentiated Human Monocytes/Macrophages by Dengue Virus: Productive Infection, Hierarchical Production of Innate Cytokines and Chemokines, and the Synergistic Effect of Lipopolysaccharide.
Y.-C. Chen and S.-Y. Wang (2002)
J. Virol. 76, 9877-9887
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Dengue Virus Selectively Induces Human Mast Cell Chemokine Production.
C. A. King, R. Anderson, and J. S. Marshall (2002)
J. Virol. 76, 8408-8419
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C.-F. Lin, H.-Y. Lei, A.-L. Shiau, H.-S. Liu, T.-M. Yeh, S.-H. Chen, C.-C. Liu, S.-C. Chiu, and Y.-S. Lin (2002)
J. Immunol. 169, 657-664
   Abstract »    Full Text »    PDF »
T Cell Responses to an HLA-B*07-Restricted Epitope on the Dengue NS3 Protein Correlate with Disease Severity.
I. Zivna, S. Green, D. W. Vaughn, S. Kalayanarooj, H. A. F. Stephens, D. Chandanayingyong, A. Nisalak, F. A. Ennis, and A. L. Rothman (2002)
J. Immunol. 168, 5959-5965
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Dengue Type 3 Virus in Plasma Is a Population of Closely Related Genomes: Quasispecies.
W.-K. Wang, S.-R. Lin, C.-M. Lee, C.-C. King, and S.-C. Chang (2002)
J. Virol. 76, 4662-4665
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Use of Recombinant Envelope Proteins for Serological Diagnosis of Dengue Virus Infection in an Immunochromatographic Assay.
A. J. Cuzzubbo, T. P. Endy, A. Nisalak, S. Kalayanarooj, D. W. Vaughn, S. A. Ogata, D. E. Clements, and P. L. Devine (2001)
Clin. Vaccine Immunol. 8, 1150-1155
   Abstract »    Full Text »    PDF »
African Swine Fever Virus Infection of Porcine Aortic Endothelial Cells Leads to Inhibition of Inflammatory Responses, Activation of the Thrombotic State, and Apoptosis.
I. Vallee, S. W. G. Tait, and P. P. Powell (2001)
J. Virol. 75, 10372-10382
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Identification of a Putative Coreceptor on Vero Cells That Participates in Dengue 4 Virus Infection.
J. d. J. Martinez-Barragan and R. M. del Angel (2001)
J. Virol. 75, 7818-7827
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Construction, Safety, and Immunogenicity in Nonhuman Primates of a Chimeric Yellow Fever-Dengue Virus Tetravalent Vaccine.
F. Guirakhoo, J. Arroyo, K. V. Pugachev, C. Miller, Z.-X. Zhang, R. Weltzin, K. Georgakopoulos, J. Catalan, S. Ocran, K. Soike, et al. (2001)
J. Virol. 75, 7290-7304
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Detection of Dengue Viral RNA Using a Nucleic Acid Sequence-Based Amplification Assay.
S.-J. L. Wu, E. M. Lee, R. Putvatana, R. N. Shurtliff, K. R. Porter, W. Suharyono, D. M. Watts, C.-C. King, G. S. Murphy, C. G. Hayes, et al. (2001)
J. Clin. Microbiol. 39, 2794-2798
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Mutagenesis of the dengue virus type 2 NS3 proteinase and the production of growth-restricted virus.
A. E. Matusan, P. G. Kelley, M. J. Pryor, J. C. Whisstock, A. D. Davidson, and P. J. Wright (2001)
J. Gen. Virol. 82, 1647-1656
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Antiviral Cytotoxic T Cells Cross-Reactively Recognize Disparate Peptide Determinants from Related Viruses but Ignore More Similar Self- and Foreign Determinants.
M. Regner, M. Lobigs, R. V. Blanden, P. Milburn, and A. Mullbacher (2001)
J. Immunol. 166, 3820-3828
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Identification of B-Cell Epitope of Dengue Virus Type 1 and Its Application in Diagnosis of Patients.
H.-C. Wu, Y.-L. Huang, T.-T. Chao, J.-T. Jan, J.-L. Huang, H.-Y. Chiang, C.-C. King, and M.-F. Shaio (2001)
J. Clin. Microbiol. 39, 977-982
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Bispecific Monoclonal Antibodies Mediate Binding of Dengue Virus to Erythrocytes in a Monkey Model of Passive Viremia.
C. S. Hahn, O. G. French, P. Foley, E. N. Martin, and R. P. Taylor (2001)
J. Immunol. 166, 1057-1065
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Potential Dengue Virus-Triggered Apoptotic Pathway in Human Neuroblastoma Cells: Arachidonic Acid, Superoxide Anion, and NF-kappa B Are Sequentially Involved.
J.-T. Jan, B.-H. Chen, S.-H. Ma, C.-I Liu, H.-P. Tsai, H.-C. Wu, S.-Y. Jiang, K.-D. Yang, and M.-F. Shaio (2000)
J. Virol. 74, 8680-8691
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Human Dengue Antibodies against Structural and Nonstructural Proteins.
K. Valdes, M. Alvarez, M. Pupo, S. Vazquez, R. Rodriguez, and M. G. Guzman (2000)
Clin. Vaccine Immunol. 7, 856-857
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Manifestation of thrombocytopenia in dengue-2-virus-infected mice.
K.-J. Huang, S.-Y. J. Li, S.-C. Chen, H.-S. Liu, Y.-S. Lin, T.-M. Yeh, C.-C. Liu, and H.-Y. Lei (2000)
J. Gen. Virol. 81, 2177-2182
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Infection of Human Cells by Dengue Virus Is Modulated by Different Cell Types and Viral Strains.
M. S. Diamond, D. Edgil, T. G. Roberts, B. Lu, and E. Harris (2000)
J. Virol. 74, 7814-7823
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Chimeric Yellow Fever/Dengue Virus as a Candidate Dengue Vaccine: Quantitation of the Dengue Virus-Specific CD8 T-Cell Response.
R. G. van der Most, K. Murali-Krishna, R. Ahmed, and J. H. Strauss (2000)
J. Virol. 74, 8094-8101
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Release of Vasoactive Cytokines by Antibody-Enhanced Dengue Virus Infection of a Human Mast Cell/Basophil Line.
C. A. King, J. S. Marshall, H. Alshurafa, and R. Anderson (2000)
J. Virol. 74, 7146-7150