CSB351Y1 Lecture Notes - Lecture 26: Attenuated Vaccine, Yellow Fever, Flavivirus
26 May 2018
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Lecture 26: Flaviviridae
Yellow Fever Virus (18th and 19th century scourges of human populations)
• Classification – prototype of flavivirus within flavivirus genus (yellow in Latin, jaundice is symptom)
Properties of Virions
• Icosahedral (50nm diameter), non-segmented +sense ssRNA (nucleocapsid), surrounded by host lipid membrane
• Capsid protein (short projections of viral glycoprotein E) on virion surface – not spikes but e-dimers/envelop T=3
Function of Flaviviral proteins
• Single ORF encodes 3 structural– capsid (C), prM (precursor to membrane) and envelop (E) proteins
• E glycoprotein – spike protruding from virion surface (attachment, hemagglutination, neutralization)
• Non structural proteins – NS1, NS3, NS5 (for replication)
- NS1 – expressed on infected cell surfaces (target for antibodies clearing virus), NS3 – helicase and protease
functions (highly conserved), NS5 – viral RNA polymerase (highly conserved)
Replication
• Attach to cells via glycoprotein E (+unknown receptor) – receptor mediated endocytosis (fusion at low pH)
• RNA released → +sense polyprotein processing on membrane → -sense→virus replication on membrane →
immature virus assembly into ER, golgi → virus maturation (golgi change in pH, prM cleavage → exocytosis
Pathology
• Yellow fever 3-6 days post bite – fever, headache, pack pain, muscle aches, nausea (remission follows but
becomes more ill with fever, dehydration, jaundice, renal failure, vomiting of blood)
• Swelling/necrosis of hepatocytes in midzone of liver– recovery shows no signs of residual scarring or cirrhosis
• Brains edema and hemorrhaging due to decrease synthesis of clotting factors by liver
Immune response
• IgG antibodies against virus (E glycoprotein spike binds IgG to block virus attachment), life-long protection
• Prevention, control and vaccine – control A. aegypti mosquitoes (nets) and attenuated vaccine in endemic areas
• Inexpensive, safe and effective (68 nt differences between 17D vaccine strain and virulent Asibi strain)
West Nile virus
• Pathogenicity – flu like illness, infections mild (nausea, vomit, eye pain, headache, rash, lymph swelling)
- Severe infections (meningitis or encephalitis, mental status changes, seizures and coma) mortality 4-11%
• Sever neurologic disease after infection risk increase for 50 or older aged
• Transmission – mosquito vector → reservoir host (enzootic birds/animals) → incidental infection (people/cows)
Zika – flaviviridae, transmitted by Aede mosquitoes (not present in Canada) or sexual transmission (corss placental
barrier, fetal infection)
• Cause mild illness of zika fever (no vaccine available, fever, rash, joint pain, death rare, symptoms last 2-7 days)
• Transmission – sylvatic cycle (mosquito,monkey) → urban cycle (mosquitoes, human) → placenta (sex)
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