Lecture 5!
Flaviviridae..
1) Properties
= Spherical enveloped virion, 40-50nm
= Inner core protein C
= Membrane / matrix protein M
= Envelope with glycoprotein peplomers (E)
= Single linear 11kb positive sense ssRNA and infectious mRNA
= 3' polyadenylated tail and 5' cap
= Cytoplasmic replication (perinuclear)
= Polyprotein from genomic RNA cleave
= 3 structural proteins
- core nucleocapsid protein C
- envelope glycoproteins M and E
= Several non-structural proteins
= Usually transmitted from a bite by the infected arthropod (mosquito or tick)
= Genomes consist of one piece of linear, single-stranded, positive sense RNA. And because the RNA is positive, the nucleic acid itself is capable of instigating an infection in the appropriate host cells. Total genome can range from 10 to 11 kilobase pairs.
2) Dengue
= most important arbovirus presently (from Southeast Asia to Americas to Pacific to Africa)
= 4 distinct serotypes based on neutralisation test: DEN-1, DEN-2, DEN-3, DEN-4; where DEN-2 shows greatest antigenic and genotypic distance from the others
= protective immunity after infection homotypic
= many infections asymptomatic
= acute infection resulting in: fever, severe headache (frontal), retro-orbital pain, nausea and vomiting
= severe muscle and bone pain
= severe arthralgia (joint sweling - mainly back) --> break bone fever
= maculopapular rash before recovery
= Dengue Haemorrahgic Fever (DHF)/Dengue Shock Syndrome (DSS)
- prior infection and age key factors (15 years and below) in DHF and DSS
- similar to yellow fever in biphasic nature:
- initial symptoms similar to DF followed by remission
- sudden deterioration of patient condition
- Symptoms include :
- severe prostration
- hypotension
- circulatory collapse
- bleeding and shock
- Bleeding
- Petechiae in skin, mucous membranes (mouth)
- Injection and punction sites
- Gastrointestinal
- Haemorrhagic pneumonia
= WHO Grading of DHF
- Grade 1: Fever with non-specific, constitutional symptoms and the only haemorrhagic manifestations being a positive tourniquet test
- Grade 2: As for Grade 1, but with specific haemorrhagic manifestations
- Grade 3: Signs of circulatory failure or hypotension
- Grade 4: Profound shock with pulse and blood pressure undetectable
= Pathogenesis
- Not well understood but still having 2 theories
1. Virulent strain theory
- some strains more virulent than others
- molecular studies show variations in sequences amongst different strains within serotypes
-early evidence pointed to DEN-2
2. Antibody enhancement
- Main theory for DHF / DSS
- Main cell target of DEN: monocytes / macrophages
- Most cases had prior infection or infants below 1 year had maternal Ab
= Possible causes of DSS / DHF
- Immune system overreacting
- Severe Acute Respiratory Syndrome
= Control means
- Insecticide
- Mosquitoes screen
- Remove stagnant water
- Quarantine
(Below: Dengue infection cycle)

3) Yellow fever
= Incubation period of 3 ~ 6 days
= Tropical disease in Latin America and Africa
= Viraemia, infectious, headache, malaise, nausea, lassitude, muscle ache (3 days)
= Flushing of head and neck, conjunctival injection, strawberry tongue
= Severe yellow fever
- Remission after acute yellow fever
- Haemorrhagic, hepatic and renal disease or failure, coffee-ground diathesis (black vomit), hypotension and shock
- Fever, vomiting, abdominal pain, dehydration, prostration
- Jaundice
- Bleeding from punction punction sites of injections and drip needles
- Massive haematemesis / haemoptysis / intra-abdominal bleeding
- Virus absent from blood, but antibody titre high, autoimmunity may play major role
- mortality of 20 ~ 50%
-survivors suffered from extended chronic jaundice before full recovery, but hepatic and renal failure may persist
= Control
- Attenuated vaccine
4) West Nile
= Mainly mild to no symptoms
= Fever, headche and body aches
= Skin rash and swollen lymph glands
= Severe symptoms include:
- Cross blood-brain barrier
- Encephalitis
- Meningitis
= Mainly in persons above 50 years
= West Nile Transmission

= Control
- insecticide
- no vaccine yet
5) References
http://www.ebi.ac.uk/interpro/IEntry?ac=IPR001122
http://carnot.utmb.edu/flavitrack/images/flavivirus_genome.png
http://www.cdc.gov/ncidod/dvbid/westnile/cycle.htm