lec 22 dengue and zika Flashcards
(31 cards)
dengue and zika are in the ____ family
flavivirus
flaviviruses are ______
+ssRNA
what determines serotype?
if there the immune system can neutralize it. Is not genetically determined. There is also genetic variation among each serotype
The dengue genome has ____ ORF and _____ cleaves the polyprotein into ___ proteins
one;
host protease;
10
the structural proteins are _____
in/on the viral particle
describe dengue NS1, 3, and 5
3 and 5 are RNA pol and helicase
NS1 is mysterious, but secreted in large amounts, thought to have to do with immune evasion/disease progression
History of dengue distribution
1950s-80s Aedes eradicated from South/Central America
HUGE outbreak after this
movement following WWII from East Asia
___% of dengue cases are subclinical
60
how many dengue cases per year?
Hemorrhagic fever?
Deaths?
50 to 100 million
720,000 are DHF
24,000 deaths
most severe cases occur in ____ people
older
Symptoms of Dengue Fever
high fever
headache
retroorbital pain
myalgias/athralgias
Fatigue
*GI - nausea/vomiting (signals complications)
cutaneous rash
hemorrhagic manifestations (low platelet count, also reduces volume of blood -> more concentrated blood -> shock)
thrmobocytopenia
DHF/DSS symptoms
increased vascular permeability -> causes severe disease
hemoconcentration
hypovolemic shock (heart doesnt pump properly)
hemorrhagic manifestations
thrombocytopenia
abdominal pain
cytokine storm
dengue symptom timeline
days 1-3 high fever and high viral load
days 4-6 immune system kicks in, low viral load/fever, decreased platelets, high hematocrit (increased permeability, potential chance of shock)
Integral Hypothesis of Dengue
Individual risk factors, viral risk factors, and epidemiological risk factors affect the manifestation of the disease
Main theories of Dengue pathology
- antibody dependent enhancement (ADE)
- T cell altered peptide ligand mediated cytokine storm (original antigenic sin - OAS)
- host genetics (innate and adaptive response)
- dengue virulence (viral genetic factors)
Support for ADE
neonates have Dengue at 6-8 months, and 2-3 years due to maternal antibodies being in the area between neutralization and enhancement
How does original antigenic sin play into Dengue pathology?
changing an outer peptide ligand can induce a response that produces cytokines but does not control the virus
ADE concept
the primary infection is asymptomatic or mild
the secondary infection from the same strain is protected but from a different serotype is actually more severe
Multiple antibodies can block binding of virions to cell receptor (neutralize)
Few antibodies (or low affinity) can enhance uptake of virions in cells with Fcgamma receptor (immune cells)
There is a gray area in which ______ is negative and _______ is positive
neutralization
enhancement
There is a relationship between pre-disease antibody titer and disease outcome. _______ titer is associated with severe disease
intermediate
Primary infection of dengue leads to (increased/reduced) risk for DENV1-4
1: reduced
2: increased
3: increased and reduced (this strain is very pathogenic as is)
4: increased risk
zika: reduced risk
Complement factors are also correlated with Dengue severity through what mechanisms
NS1 can cleave complement
Activates MBL, properdin, C4a, C3a, C5a, C5-C9 MAC, CFD
inhibits C1-INH, CFH (inhibitors of complement)
Sanofi vaccine
reverse genetics of yellow fever vaccine, replace Envelope and membrane to Dengue serotypes
This vaccine is only effective in those with previous Dengue infection since it does not activate T cell response
CDC-inviragen vaccine
Dengue 2 attenuated virus with each serotypes membrane/envelope protein
perfect for DENV2, ok for 1, doesn’t work for 3, unknown for 4
