CSB351Y1 Lecture Notes - Lecture 27: Viral Hemorrhagic Fever, Tourniquet Test, Viremia

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Lecture 27: Flaviviridae 2
Dengue Fever Virus
Icosahedral, ssRNA, enveloped, 50nm diameter, origin unknown, highly adapted to mosquito hosts, humans first
came in contact with DFV when forests cleared for human settlements (jungle human populations)
3 structural proteins (nucleocapsid (c), membrane associated protein (M) and envelope protein (E)) responsible
for neutralization, fusion, interaction with virus receptors = associated with E protein
Replication Cycle
Entry (receptor binding) by endocytosis, E protein fuse to membrane of endosome, release RNA, transcription (-
sense), polyprotein processing protease cleavage in host membrane/ER genome packaging (+ sense) with
capsid proteins on surface of ER, prM and E associated with inside of ER immature virus particle prM
conformation change that clips mature virus particle
Dimeric or trimeric conformation of E glycoprotein
prM (precursor membrane protein) associated with domain II of E protein and acts as chaperone for folding E
and preventing premature fusion of virus
- Contains furin protease cleavage site cleaved into c-terminal M portion (transmembrane domain remains
with virus) and n-terminal fragment dissociates upon release of virus from infected cell
Epidemiology
Exist in nature forest cycle involves canopy-dwelling mosquitoes and primates, rural cycle has Asia and Pacific
humans and urban cycle (most important for us)
Transmission bite mosquito all 4 serotypes cause high levels of viremia (virus also acquired by mosquitos)
No apparent effect on mosquito (life long infection however) but female mosquitoes transmit transovarily (eggs)
Distribution and host range worldwide tropics, southern Saharan Africa, half million hospitalized (children)
No vaccine or antiviral drug available
4 grades of DHF (dengue hemorrhagic fever)
1. Fever and nonspecific symptoms, positive tourniquet test is only hemorrhagic manifestation
2. Grade 1 + spontaneous bleeding
3. Signs of circulatory failure (rapid/week pulse, change in blood pressure, hypotension, cold/clammy skin)
4. Profound shock (no heart pulse and blood pressure goes down near death)
Viral Risk Factors of DHF Pathogenesis
Virus genotype epidemic potential: how much virus in blood (viremia level), infectivity (how much mosquitos)
Virus serotype can determine how sick you can be DHF risk is greatest for DEN-2, DEN-3, DEN-4 and DEN-1
Tropism (which tissues are affected)
Primary virus replication site in phagocytic monocytes (immune cell) liver, lungs, kidney, lymph, stomach
Encephalopathy reported but dengue viruses cannot cross BBB into CNS; DHF or DSS (dengue shock syndrome)
Antibody-dependent enhancement (ADE)
DHF, develop immune (antibodies) for subtype to prevent virus binding to macrophage cells of host to gain entry
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