Fever, headache, joint pains, acute phase for 3-7 days, 50-100mil cases / yr
5 of 34
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
6 of 34
What is its genome reminiscent of?
Hep C
7 of 34
Two main gene sections?
Structual Protein genes (SP), Non-structural protein genes
Ab bound to dengue + Fc receptor on host / DC-SIGN on host
19 of 34
How do virus particles mature?
Host furin proteases cleave prM on particle surface to form M
20 of 34
What happens to pr protein?
It is cleaved off the particle to different extents, to help with immune evasion
21 of 34
How does protein synthesis occur?
Proteolytic processing - processing of polyprotein into multiple proteins (structural and non-structural)
22 of 34
Where does it occur?
In ER lumen and cytoplasm
23 of 34
Why is it hard to study DHF pathogenesis?
No suitable animal model
24 of 34
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
25 of 34
What is the immune enhancement hypothesis?
Immune system exacerbates disease. Pre-existing cross-reactive Abs, aticvated memory CTLs
26 of 34
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
27 of 34
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
28 of 34
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.
29 of 34
What vaccine is used?
Genetically engineered - yellow fever vaccine used as template (very safe). Reverse genetics, prM + E genes added
30 of 34
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
31 of 34
What is the Ab response to a mature virion?
Ab specific for envelope protein - neutralisation OR Ab-dependent enhancement
32 of 34
What is the Ab response to an immature virion?
Ab specific for pre-M protein - Ab-dependent enhancement, enhances uptake
33 of 34
What is the Ab response to NS1 protein on cell membrane?
Comments
No comments have yet been made