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DENGUE VIRUS
Case-study 
17 year-old female admitted into Princeton Plainsborough Hospital. The 
patient present the following symptoms...
Case-study
BACKGROUND INFORMATION 
• Word origin may be derived from Swahili or Spanish 
• 3 forms of dengue: 
• Dengue fever (DF), d...
GLOBAL DISTRIBUTION 
(Comprehensive Guidelines for Prevention and Control of Dengue and Dengue Haemorrhagic Fever, 2011) 
...
EPIDEMIOLOGY 
• ~ 50-100 million infections occur worldwide, 0.5 million hospitalized for DHF 
• ~ 90% are children under ...
EPIDEMIOLOGY CONT’D 
• Ae. aegypti strongly attracted to humans, domesticated, and is a nervous feeder 
• Bites more than ...
PREVENTION 
• Key is disease surveillance to detect epidemics 
• Dengue-endemic regions should be educated about the virus...
EVOLUTION 
• Genus: Flavivirus 
• Diverse 
• 4 serotypes 
• 1970: Central America 
and Africa (DEN 1 & 2) 
Southeast Asia ...
VIRUS STRUCTURE & COMPONENTS 
Dengue 
• Class IV: Positive Sense Single Stranded 
RNA Virus 
DNA Components 
• Internal St...
TRANSMISSION 
• Mosquito (female mosquito) 
• Possibly through blood transfusions 
• Human incubation period ~ 4 days 
• V...
THE DENGUE VIRUS 
Envelope Proteins 
Lipid Bilayer 
Capsid 
RNA Genome 
DENGUE LIFE CYCLE 
1. 1. Receptor-Mediated Endocyt...
DENGUE LIFE CYCLE 
Infected Mosquito Biting
DENGUE LIFE CYCLE 
Extracellular Matrix
DENGUE LIFE CYCLE 
Cognate receptor 
Dengue virus 
Extracellular Space 
ERnecdeopctyotro Bsiisnding 
Cell Membrane 
Cytopl...
DENGUE LIFE CYCLE 
Endosome 
Proton Pump 
Fusion 
H+ 
H+ 
CLoonwfoerrmeda tpioHnal Change 
Cytoplasm
DENGUE LIFE CYCLE 
Endosome 
Proton Pump H+ 
H+ 
FCuosnifoonrmational Change 
Cytoplasm
DENGUE LIFE CYCLE 
NFuusciloenocapsid Release 
Cytoplasm
DENGUE LIFE CYCLE 
Nucleocapsid Release Cytoplasm
DENGUE LIFE CYCLE 
Cytoplasm 
Viral RNA 
Viral RNA Translation 
Ribosomes 
Rough Endoplasmic Reticulum
DENGUE LIFE CYCLE 
Cytoplasm 
Viral RNA 
Viral RNA Translation 
Ribosomes 
Rough Endoplasmic Reticulum
DENGUE LIFE CYCLE 
Cytoplasm 
Envelope Proteins 
Viral RNA Translation 
Capsid Proteins 
RNA dependent 
RNA Polymerase 
Ro...
DENGUE LIFE CYCLE 
Cytoplasm 
RdRp 
Envelope Proteins 
Viral RNA Translation 
Capsid Proteins 
RNA dependent 
RNA Polymera...
DENGUE LIFE CYCLE 
RNA Replication 
Cytoplasm 
RdRp 
RNA dependent RNA Polymerase 
SDionugblel es tsrtarnanddeded R RNNAA
DENGUE LIFE CYCLE 
RNA Transcription 
Cytoplasm 
Double stranded RNA 
RdRp
DENGUE LIFE CYCLE 
Cytoplasm 
Viral RNA 
Viral RNA Translation 
Ribosomes 
Rough Endoplasmic Reticulum
DENGUE LIFE CYCLE 
Cytoplasm 
Viral RNA 
Viral RNA Translation 
Ribosomes 
Rough Endoplasmic Reticulum
R 
DENGUE LIFE CYCLE 
Cytoplasm 
Envelope Proteins 
Viral RNA Translation 
Capsid Proteins 
RdRp 
Rough Endoplasmic Reticu...
DENGUE LIFE CYCLE 
Cytoplasm 
Viral RBNuAd dTirnagnslation 
Cell Membrane 
Rough Endoplasmic Reticulum
DENGUE LIFE CYCLE 
RER 
Golgi Apparatus
DENGUE LIFE CYCLE 
Golgi Apparatus 
Furin Cleavage 
Furin
Golgi Apparatus Cytoplasm 
Cognate receptor 
Extracellular Space 
Molecular Structure 
• External Structure : icosahedral ...
PATHOPHYSIOLOGY 
Complement 
Activation 
ADE of virus 
T-cell 
Immunology 
Plasma Leakage Bleeding Diathesis 
Hypovolemic ...
PATHOPHYSIOLOGY- ADE Activation 
Main Result: Increase in virus replication and numbers 
Heterotypic antibodies 
- Low con...
PATHOPHYSIOLOGY- ADE Activation 
Main Result: Increase in virus replication and numbers 
Heterotypic antibodies 
- Low con...
PATHOPHYSIOLOGY- ADE Activation 
Main Result: Increase in virus replication and numbers 
Heterotypic antibodies 
- Low con...
PATHOPHYSIOLOGY- Complement Activation 
• NS1- Glycoprotein secreted by dengue 
infected cells 
• Activation of innate imm...
PATHOPHYSIOLOGY- T-Lymphocyte Pathogenesis 
Primary Infection 
DENV-1 
T- cell selection 
(Dejnirattisai et al., 2010)
PATHOPHYSIOLOGY- T-Lymphocyte Pathogenesis 
Primary Infection 
DENV-1 
Secondary Infection 
T- cell selection 
DENV-2 Clon...
PATHOPHYSIOLOGY- T-Lymphocyte Pathogenesis 
Primary Infection 
DENV-1 
Secondary Infection 
T- cell selection 
DENV-2 Clon...
ENDOTHELIAL CELL ACTIVATION 
Cytokines induce changes in 
endothelial morphology: 
• Loss of vascular integrity 
• Increas...
COAGULOPATHY 
Loss of Plasma 
Components 
- Platelets 
- Plasma 
fibrinogen 
Immune-mediated 
Destruction of 
Platelets 
G...
SYMPTOMS 
Dengue Fever and Dengue Hemorrhagic Fever 
Febrile: 
• Hallmark trait is fever 
• Convulsions may occur due to h...
Case-study 
Back at Princeton Plainsborough, House has ordered his team to perform an 
endoscopy to check for internal hem...
DIAGNOSIS 
• Clinical symptoms 
• Often misdiagnosed with influenza, 
malaria, Typhoid fever, Leptospirosis 
• Travel hist...
ANTIVIRAL THERAPY 
AG129 Mouse Model 
• deficient for interferon-α/β/ϒ receptors 
• one of only models that permit infecti...
LIVE-ATTENUATED VACCINATION 
DENVax 
DENVax 
• based on the PDK53 DENV-2 backbone 
• containing pre-membrane & E genes of ...
CHIMERIC LIVE-ATTENUATED VACCINATION 
ChimeriVax Vaccine (Sanofi Pasteur) 
• uses 17D yellow fever vaccine virus 
• Phase ...
REFERENCES 
Avirutnan, P., Zhang, L., Punyadee, N., Manuyakorn, A., Puttikhunt, C., Kasinrerk, W., Malasit, P., Atkinson, ...
REFERENCES 
Halstead, S., and O'rourke, E. (1977). Dengue viruses and mononuclear phagocytes. I. Infection enhancement 
by...
REFERENCES 
Nishiura, H., & Halstead, S. (2007). Natural History of Dengue Virus (DENV)—1 and DENV—4 
Infections: Reanalys...
REFERENCES 
Zompi, S., and Harris, E. (2013). Original antigenic sin in dengue revisited. Proceedings Of The 
National Aca...
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Dengue Virus Overview

An overview on Dengue Virus, its epidemiology, prevention, evolution, structure & components, transmission, life cycle, pathophysiology, coagulopathy, symptoms, diagnosis, antiviral drugs/vaccination. Performed by Catherine Duong, Diana Elborno, Zehraa Cheaib, Michael South, Veronica Nguyen & Zachary Jilesen at McMaster University, Virology, Fall of 2014.

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Dengue Virus Overview

  1. 1. DENGUE VIRUS
  2. 2. Case-study 17 year-old female admitted into Princeton Plainsborough Hospital. The patient present the following symptoms: • High Fever • Severe nausea • Mild nosebleeds • Joint pain • New appearance of skin rashes
  3. 3. Case-study
  4. 4. BACKGROUND INFORMATION • Word origin may be derived from Swahili or Spanish • 3 forms of dengue: • Dengue fever (DF), dengue haemorrhagic fever (DHF), and dengue shock syndrome (DSS) • Arboviral infection transmitted by the Aedes aegypti mosquito • Originates in African forests independent of humans  breeds in water storage containers  slave and commerce trade brought it to South-East Asia & “New World” in 17th-19th centuries  1800 in global tropical coasts (Comprehensive Guidelines for Prevention and Control of Dengue and Dengue Haemorrhagic Fever, 2011)
  5. 5. GLOBAL DISTRIBUTION (Comprehensive Guidelines for Prevention and Control of Dengue and Dengue Haemorrhagic Fever, 2011) • Found in tropical and subtropical regions of the world, 2.5 billion at risk • Endemic in more than 100 countries in the WHO regions: • Africa, Americas, Eastern Mediterranean, South-East Asia, and Western Pacific • South-East Asia and Western Pacific regions are the most seriously affected
  6. 6. EPIDEMIOLOGY • ~ 50-100 million infections occur worldwide, 0.5 million hospitalized for DHF • ~ 90% are children under 5 years • Classical DF more common in adults •  frequency of epidemics observed, infection rates of the previously unexposed is 40% - 50%, can reach 80% - 90% • Needs coincidence of many vector mosquitoes, many people with no immunity to ¼ virus types, and opportunity for contact • Infection with any 1 of 4 serotypes  lifelong immunity to that 1 serotype • Provides 1-3 years of cross-protection against other 3 serotypes • Reoccurring infection with different serotypes  severe dengue (DHF/DSS) (CDC, 2014)
  7. 7. EPIDEMIOLOGY CONT’D • Ae. aegypti strongly attracted to humans, domesticated, and is a nervous feeder • Bites more than one host to complete blood meal and gonotropic cycle • Breeds in safe clean water, feeds at dusk and dawn • Results in multiple cases in cities • Transmission usually occurs in rainy seasons when humidity and temperature are conducive for survival and breeding • transport, human contact, urbanization, drinking water supply in rural areas brought DF to urban and rural areas globally (Comprehensive Guidelines for Prevention and Control of Dengue and Dengue Haemorrhagic Fever, 2011)
  8. 8. PREVENTION • Key is disease surveillance to detect epidemics • Dengue-endemic regions should be educated about the virus, recognize symptoms, and prevent transmission: • Regularly remove sources of stagnant water to prevent breeding • Use mosquito repellent, coils, and nets • Wear long, loose clothing in the daytime • Use nets and coils on those with DF to prevent mosquitoes transmitting infections • Stay in AC or well-screened housing • Infected mosquitoes like to live in/around homes with clean water
  9. 9. EVOLUTION • Genus: Flavivirus • Diverse • 4 serotypes • 1970: Central America and Africa (DEN 1 & 2) Southeast Asia (Den1-4) • 2004: Worldwide (Den1- 4) • 65% genome shared • Clinical characteristics conserved (Holmes,E & Twiddy, S, 2003)
  10. 10. VIRUS STRUCTURE & COMPONENTS Dengue • Class IV: Positive Sense Single Stranded RNA Virus DNA Components • Internal Structure: 10 genes (3 structural and 7 non-structural ) Molecular Structure • External Structure : icosahedral & 50 nm in diameter (Kuhn, R.J. et al. , 2002)
  11. 11. TRANSMISSION • Mosquito (female mosquito) • Possibly through blood transfusions • Human incubation period ~ 4 days • Viremia lasts ~5 days • During viremia biting mosquitos are susceptible to infection • Mosquitos incubation period ~8-12 days, which then it is infectious for life • Virus resides in salivary glands of infected mosquito (anti-clotting factors, ect) (Nishiura, H., & Halstead, 2007; Rodenhuis-Zybert, 2011).
  12. 12. THE DENGUE VIRUS Envelope Proteins Lipid Bilayer Capsid RNA Genome DENGUE LIFE CYCLE 1. 1. Receptor-Mediated Endocytosis 2. 2. Fusion 3. 3. Nucleocapsid Release 4. 4. RNA Replication 5. 5. Translation 6. 6. Budding 7. 7. Furin Cleavage 8. 8. Progeny Release (Martina, B. et al, 2009)
  13. 13. DENGUE LIFE CYCLE Infected Mosquito Biting
  14. 14. DENGUE LIFE CYCLE Extracellular Matrix
  15. 15. DENGUE LIFE CYCLE Cognate receptor Dengue virus Extracellular Space ERnecdeopctyotro Bsiisnding Cell Membrane Cytoplasm
  16. 16. DENGUE LIFE CYCLE Endosome Proton Pump Fusion H+ H+ CLoonwfoerrmeda tpioHnal Change Cytoplasm
  17. 17. DENGUE LIFE CYCLE Endosome Proton Pump H+ H+ FCuosnifoonrmational Change Cytoplasm
  18. 18. DENGUE LIFE CYCLE NFuusciloenocapsid Release Cytoplasm
  19. 19. DENGUE LIFE CYCLE Nucleocapsid Release Cytoplasm
  20. 20. DENGUE LIFE CYCLE Cytoplasm Viral RNA Viral RNA Translation Ribosomes Rough Endoplasmic Reticulum
  21. 21. DENGUE LIFE CYCLE Cytoplasm Viral RNA Viral RNA Translation Ribosomes Rough Endoplasmic Reticulum
  22. 22. DENGUE LIFE CYCLE Cytoplasm Envelope Proteins Viral RNA Translation Capsid Proteins RNA dependent RNA Polymerase Rough Endoplasmic Reticulum
  23. 23. DENGUE LIFE CYCLE Cytoplasm RdRp Envelope Proteins Viral RNA Translation Capsid Proteins RNA dependent RNA Polymerase Proteases Peptidases Cell Membrane Rough Endoplasmic Reticulum
  24. 24. DENGUE LIFE CYCLE RNA Replication Cytoplasm RdRp RNA dependent RNA Polymerase SDionugblel es tsrtarnanddeded R RNNAA
  25. 25. DENGUE LIFE CYCLE RNA Transcription Cytoplasm Double stranded RNA RdRp
  26. 26. DENGUE LIFE CYCLE Cytoplasm Viral RNA Viral RNA Translation Ribosomes Rough Endoplasmic Reticulum
  27. 27. DENGUE LIFE CYCLE Cytoplasm Viral RNA Viral RNA Translation Ribosomes Rough Endoplasmic Reticulum
  28. 28. R DENGUE LIFE CYCLE Cytoplasm Envelope Proteins Viral RNA Translation Capsid Proteins RdRp Rough Endoplasmic Reticulum
  29. 29. DENGUE LIFE CYCLE Cytoplasm Viral RBNuAd dTirnagnslation Cell Membrane Rough Endoplasmic Reticulum
  30. 30. DENGUE LIFE CYCLE RER Golgi Apparatus
  31. 31. DENGUE LIFE CYCLE Golgi Apparatus Furin Cleavage Furin
  32. 32. Golgi Apparatus Cytoplasm Cognate receptor Extracellular Space Molecular Structure • External Structure : icosahedral Progeny Release
  33. 33. PATHOPHYSIOLOGY Complement Activation ADE of virus T-cell Immunology Plasma Leakage Bleeding Diathesis Hypovolemic Shock (Nishiura, H., & Halstead, 2007; Halstead & O’rourke, 1977) ).
  34. 34. PATHOPHYSIOLOGY- ADE Activation Main Result: Increase in virus replication and numbers Heterotypic antibodies - Low concentration - Partial neutralization - Ie. prM (Halstead et al. 2010)
  35. 35. PATHOPHYSIOLOGY- ADE Activation Main Result: Increase in virus replication and numbers Heterotypic antibodies - Low concentration - Partial neutralization - Ie. prM Virus uptake - Delivery to Fcɣ receptor cells (Halstead et al. 2010)
  36. 36. PATHOPHYSIOLOGY- ADE Activation Main Result: Increase in virus replication and numbers Heterotypic antibodies - Low concentration - Partial neutralization - Ie. prM Virus uptake - Delivery to Fcɣ receptor cells Replication - Increased viral replication compared to virus alone (Halstead et al. 2010)
  37. 37. PATHOPHYSIOLOGY- Complement Activation • NS1- Glycoprotein secreted by dengue infected cells • Activation of innate immune system on endothelial cell surface Anaphylatoxins 1) Classical complement 2) Alternative complement Result: 1) Apoptosis of endothelial cell 2) Inflammation = CYTOKINES! (Guzman & Kouri, 2002)
  38. 38. PATHOPHYSIOLOGY- T-Lymphocyte Pathogenesis Primary Infection DENV-1 T- cell selection (Dejnirattisai et al., 2010)
  39. 39. PATHOPHYSIOLOGY- T-Lymphocyte Pathogenesis Primary Infection DENV-1 Secondary Infection T- cell selection DENV-2 Clonal Expansion Cross-Reaction (Dejnirattisai et al., 2010)
  40. 40. PATHOPHYSIOLOGY- T-Lymphocyte Pathogenesis Primary Infection DENV-1 Secondary Infection T- cell selection DENV-2 Clonal Expansion Cross-Reaction TNF-α IFN-ɣ IL-2 CYTOKINE STORM (Dejnirattisai et al., 2010)
  41. 41. ENDOTHELIAL CELL ACTIVATION Cytokines induce changes in endothelial morphology: • Loss of vascular integrity • Increased adhesion molecules • Increased cytokine production http://www.scielo.br/img/revistas/rb/v43n6/en_a13fig01.jpg IMPLICATIONS: Plasma leakage (Manson et al. 2003) Edema Hypovolemic shock Thrombocytopenia
  42. 42. COAGULOPATHY Loss of Plasma Components - Platelets - Plasma fibrinogen Immune-mediated Destruction of Platelets Glycocalyx Damage - Anti-coagulation via heparan sulphate (Sellahewa, K, 2012)
  43. 43. SYMPTOMS Dengue Fever and Dengue Hemorrhagic Fever Febrile: • Hallmark trait is fever • Convulsions may occur due to high fever (DHF) • Thrombocytopenia, leukopenia (levels more drastic with DHF) Critical • Plasma leakage into pleural cavities, ascites (DHF) • Subnormal temperatures, defervescence • Varying degrees of hemorrhage (worsened for DHF) Recovery • Reabsorption of accumulated fluids • Improved vital signs • Important to monitor (CDC, 2010)
  44. 44. Case-study Back at Princeton Plainsborough, House has ordered his team to perform an endoscopy to check for internal hemorrhaging … New symptom: Vomiting blood, excessive bleeding in gastrointestinal tract… Complications: Excessive loss of fluid, increased lymphatic return, overcompensation of cardiovascular/adrenal/renal mechanisms, anoxia = DENGUE SHOCK SYNDROME
  45. 45. DIAGNOSIS • Clinical symptoms • Often misdiagnosed with influenza, malaria, Typhoid fever, Leptospirosis • Travel history • Viral markers IgG, IgM, and NS1 • Laboratory confirmation: • IgM Capture ELISA • NS-1 specific assays • Lateral flow test to detect IgM & IgG antibody, NS1 antigen (CDC, 2010; Mayo Clinic, 2013)
  46. 46. ANTIVIRAL THERAPY AG129 Mouse Model • deficient for interferon-α/β/ϒ receptors • one of only models that permit infection by all 4 serotypes • used to target virus entry, membrane fusion, RNA genome DENVax replication, assembly, & release from infected cell • targets protein E to interfere with viral replication 7-deaza-2′- C-methyl- adenosine (Schul et al., 2007; Wilder-Smith et al., 2010) N-nonyl-deoxynojirimycin 6-O-butanoyl castanospermine • treatment tested in viremia mouse model (AG129 mice) during acute phase • block viral replication
  47. 47. LIVE-ATTENUATED VACCINATION DENVax DENVax • based on the PDK53 DENV-2 backbone • containing pre-membrane & E genes of serotypes 1-4 • tested in cynomolgus macaques • Immunogenicity & efficacy results LATV (Durbin et al., 2013; Osorio et al., 2011) • contains 30 nucleotide deletion; tetravalent • tested in flavivirus-naïve adults • no significant difference in adverse events between vaccines and placebo-recepients • Race factor influencing infectivity of LATV virus
  48. 48. CHIMERIC LIVE-ATTENUATED VACCINATION ChimeriVax Vaccine (Sanofi Pasteur) • uses 17D yellow fever vaccine virus • Phase I, II, III DENVax • shows 57% overall efficacy • reduction of hospitalization by 80% • 89% reduction of dengue haemorrhagic fever Mahidol (Fink & Shi, 2014; Wilder-Smith et al., 2010) • PDK-53 DEN-2 backbone • Phase 1 trial (U.S. & Columbia) • protective when administered in monkeys and mice
  49. 49. REFERENCES Avirutnan, P., Zhang, L., Punyadee, N., Manuyakorn, A., Puttikhunt, C., Kasinrerk, W., Malasit, P., Atkinson, J., and Diamond, M. (2007). Secreted NS1 of dengue virus attaches to the surface of cells via interactions with heparan sulfate and chondroitin sulfate E. Plos Pathogens 3, 183. Avirutnan, P., Punyadee, N., Noisakran, S., Komoltri, C., Thiemmeca, S., Auethavornanan, K., Jairungsri, A., Kanlaya, R., Tangthawornchaikul, N., and Puttikhunt, C. et al. (2006). Vascular leakage in severe dengue virus infections: a potential role for the nonstructural viral protein NS1 and complement. Journal Of Infectious Diseases 193, 1078-1088. Centers for Disease Control and Prevention. (2010). Dengue. Retrieved from: http://www.cdc.gov/dengue/clinicallab/clinical.html Comprehensive Guidelines for Prevention and Control of Dengue and Dengue Haemorrhagic Fever: Revised and Expanded Edition. (2011). Retrieved 13 October 2014, from http://apps.searo.who.int/pds_docs/B4751.pdf?ua=1 Dejnirattisai, W., Jumnainsong, A., Onsirisakul, N., Fitton, P., Vasanawathana, S., Limpitikul, W., Puttikhunt, C., Edwards, C., Duangchinda, T., and Supasa, S. et al. (2010). Cross-reacting antibodies enhance dengue virus infection in humans. Science 328, 745-748. Dejnirattisai, W., Jumnainsong, A., Onsirisakul, N., Fitton, P., Vasanawathana, S., Limpitikul, W., Puttikhunt, C., Edwards, C., Duangchinda, T., and Supasa, S. et al. (2010). Enhancing cross-reactive anti-prM dominates the human antibody response in dengue infection. Science (New York, NY) 328. Fink, M. (2005). Dengue. Textbook of critical care (Philadelphia: Elsevier Saunders). Guzman, M., and Kouri, G. (2002). Dengue: an update. The Lancet Infectious Diseases 2, 33-42.
  50. 50. REFERENCES Halstead, S., and O'rourke, E. (1977). Dengue viruses and mononuclear phagocytes. I. Infection enhancement by non-neutralizing antibody. The Journal Of Experimental Medicine 146, 201-217. Halstead, S., Mahalingam, S., Marovich, M., Ubol, S., and Mosser, D. (2010). Intrinsic antibody-dependent enhancement of microbial infection in macrophages: disease regulation by immune complexes. The Lancet Infectious Diseases 10, 712-722. Holmes, E. & Twiddy, S. (2003). The origin, emergence an evolutionary genetics of dengue virus. Infections, Genetics and Evolution, 3(1), 1928. In, L. (2003). Howard Hughes Medical Institute Kuhn, R.J. et al. (2002). Implications for flavivirus organization, maturation, and fusion. Cell, 108, 717-725. Manson, P., Cook, G., Zumla, A., and Manson, P. (2003). Manson's tropical diseases (London: Saunders). Martina, B., Koraka, P., & Osterhaus, A. (2009). Dengue virus pathogenesis: an integrated view.Clinical Microbiology Reviews, 22(4), 564--581. Nature.com,. (2014). Retrieved 14 October 2014, from http://www.nature.com/scitable/content/ne0000/ne0000/ne0000/ne0000/22400749/F2_dengue_2_1.jpg Nimmannitya, S. (1999). Dengue hemorrhagic fever: disorders of hemostasis. 184-187.
  51. 51. REFERENCES Nishiura, H., & Halstead, S. (2007). Natural History of Dengue Virus (DENV)—1 and DENV—4 Infections: Reanalysis of Classic Studies. Journal Of Infectious Diseases, 195(7), 1007--1013. Rodenhuis-Zybert, I., Wilschut, J., & Smit, J. (2010). Dengue virus life cycle: viral and host factors modulating infectivity. Cellular And Molecular Life Sciences, 67(16), 2773--2786. Sellahewa, K. (2012). Pathogenesis of Dengue Haemorrhagic Fever and Its Impact on Case Management. ISRN Infectious Diseases 2013. Seynhaeve, A., Vermeulen, C., Eggermont, A., and ten Hagen, T. (2006). Cytokines and vascular permeability. Cell Biochemistry And Biophysics 44, 157-169. Srikiatkhachorn, A., and others, (2009). Plasma leakage in dengue haemorrhagic fever. Thromb Haemost 102, 1042-9. Srikiatkhachorn, A., and others, (2009). Plasma leakage in dengue haemorrhagic fever. Thromb Haemost 102, 1042-9. Stoermer, K., and Morrison, T. (2011). Complement and viral pathogenesis. Virology 411, 362-373.
  52. 52. REFERENCES Zompi, S., and Harris, E. (2013). Original antigenic sin in dengue revisited. Proceedings Of The National Academy Of Sciences 110, 8761-8762.

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An overview on Dengue Virus, its epidemiology, prevention, evolution, structure & components, transmission, life cycle, pathophysiology, coagulopathy, symptoms, diagnosis, antiviral drugs/vaccination. Performed by Catherine Duong, Diana Elborno, Zehraa Cheaib, Michael South, Veronica Nguyen & Zachary Jilesen at McMaster University, Virology, Fall of 2014.

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