L8 - Dengue Virus

RNA (+ve sense)
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How many serotypes?
4 (DENV 1-4)
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What is its normal transmission cycle called?
Sylvatic/enzootic (Mosquito < -> primate
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What are the two types of dengue disease?
Classical dengue fever (DF), Dengue Haemorrhagic Fever (DHF)
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Symptoms of DF
Fever, headache, joint pains, acute phase for 3-7 days, 50-100mil cases / yr
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Symptoms of DHF
Initial fever leads to sudden collapse, acute increase in vascular permeability, may progress to severe shock syndrome, primarily a disease of under 15, 10% mortality, 0.5mil cases / yr
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What is its genome reminiscent of?
Hep C
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Two main gene sections?
Structual Protein genes (SP), Non-structural protein genes
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What are the SPs?
C, M, E
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What does C do?
Forms nucleocapsid with RNA
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What does M do?
Membrane protein
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What does E do?
Envelope protein
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Main NSPs?
NS1, NS3, NS5
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What does NS1 do?
Secreted - basis of diagnostic test in blood
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What does NS3 do?
Protease and Helicase
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What does NS5 do?
RdRp, methyltransferase
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What is its lifecycle similar to?
Hep C
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1) Virus outside cell. 2) Attachment. 3) Endocytosis. 4) Uncoating. 5) Translation and processing. 6) Formation of replication complex. 7) Nucleocapsid formation. 8) Particle assembly. 9) Virus maturation. 10) Virus release
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What receptors mediate attachment?
Ab bound to dengue + Fc receptor on host / DC-SIGN on host
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How do virus particles mature?
Host furin proteases cleave prM on particle surface to form M
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What happens to pr protein?
It is cleaved off the particle to different extents, to help with immune evasion
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How does protein synthesis occur?
Proteolytic processing - processing of polyprotein into multiple proteins (structural and non-structural)
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Where does it occur?
In ER lumen and cytoplasm
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Why is it hard to study DHF pathogenesis?
No suitable animal model
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DHF pathogenesis mechanism
1) Virus targets cells for replication (skin dendritic cells -> monocytes). 2) viraemia and fever occurs for 2-12 days. Pro-inflammatory cytokine mediated. 3) Secondary infection by different serotypes gives severe disease
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What is the immune enhancement hypothesis?
Immune system exacerbates disease. Pre-existing cross-reactive Abs, aticvated memory CTLs
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What is Ab-dependent enhancement of infection?
When secondary infection occurs with a different serotype - the Abs are cross-reactive but non-neutralising. The complex is taken up by monocytes which become infected
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How do T Cells exacerbate infection?
Secondary infection - the MHC peptide doesnt fit well with the TCR, so there is a partial response - different cytokine products, inefficient lysis of infected cell
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What are the challenges affecting dengue virus control?
High transmissibility due to mosquitos, globalisation. Hyperendemicity. Inducing partial immunity may predispose to more severe disease of different serotypes. No animal model. tetravalent vaccine production is difficult.
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What vaccine is used?
Genetically engineered - yellow fever vaccine used as template (very safe). Reverse genetics, prM + E genes added
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When should/shouldn't you have the vaccine?
Should - if you have previously had dengue it acts as a booster. Shouldn't - if you haven't - predisposes you to more severe disease
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What is the Ab response to a mature virion?
Ab specific for envelope protein - neutralisation OR Ab-dependent enhancement
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What is the Ab response to an immature virion?
Ab specific for pre-M protein - Ab-dependent enhancement, enhances uptake
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What is the Ab response to NS1 protein on cell membrane?
Ab specific for NS1 - Complement dependent lysis.
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Card 2


How many serotypes?


4 (DENV 1-4)

Card 3


What is its normal transmission cycle called?


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Card 4


What are the two types of dengue disease?


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Card 5


Symptoms of DF


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