Specific Viral Families: Flaviviridae


Flaviviridae

The flaviviruses are enveloped, polyhedral, (+) sense RNA viruses that are transmitted by mosquitoes and ticks. The viruses produce a variety of encephalitides or fevers in humans. The yellow fever virus is a flavivirus that cause a haemorrhagic fever—in which blood vessels in the skin, mucous membranes and internal organs bleed uncontrollably. Hepatitis C infection is also caused by a flavivirus.

Important 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—infectious mRNA

    · Polyadenylated tail and 5’ cap

    · Cytoplasmic replication

    · Polyprotein from genomic RNA cleaved

    · 3 structural proteins

    · Several non-structural proteins

Dengue Virus

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  · Most important arbovirus presently.

    · Transmitted through the bite of a female Aedes aegypti mosquito (the vector).

    · 4 distinct serotypes based on neutralisation test.

    · DEN-1, DEN-2, DEN-3 and DEN-4

    · DEN-2 shows greatest antigenic and genotypic distance from the others.

    · Protective immunity after infection homotypic.


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Dengue Infectious Cycle

Classic Dengue begins suddenly with an influenza syndrome consisting of fever, malaise, cough, and headache. Severe pains in muscles and joints occur. Enlarged lymph nodes, a masculopapular rash, and leukopenia are common. After a week or so, the symptoms regress but weakness may persist. Although unpleasant, this typical form of dengue is rarely fatal and has few sequelae.

Dengue Haemorrhagic Fever (DHF) is a much more severe disease, with a fatality rate that approaches 10%. The initial picture is the same as classic dengue, but then shock and haemorrhage, especially into the gastrointestinal tract and skin, develop. Dengue haemorrhagic fever occurs particularly in southern Asia, whereas the classical form is found in tropical areas worldwide.

Haemorrhagic Shock Syndrome (DSS) is due to the production of large amounts of cross-reacting antibody at the time of a second dengue infection. The pathogenesis is as dollows: The patient recovers from classic dengue caused by one of the four serotypes, and antibody against that serotype is produced. When the patient is infected with another serotype of dengue virus, an anamnestic, heterotypic response occurs, and large amounts of cross-reacting antibody to the first serotype are produced.

Pathogenesis of DHF/DSS

  1. Virulent strain theory

a. Some strains are more virulent than others

b. Molecular studies show variations in sequences amongst different strains within serotypes

c. Early evidence pointed to DEN-2

  2. Antibody enhancement

a. Main theory for DHF/DSS

b. Main cell target of DEN: Monocytes and macrophages

c. Most cases of DHF/DSS had prior infection or infants below 1 year had maternal Ab.

d. Monkey experiments showed similar enhancement.

Control of Dengue Virus

    · No antiviral therapy or vaccine for dengue is available.

    · Outbreaks are controlled by using insecticides and draining stagnant water that serves as the breeding ground for mosquitoes.

    · Personal protection includes using mosquito repellent and wearing clothing that covers the entire body.

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Yellow Fever Virus

http://pathmicro.med.sc.edu/mhunt/yellow%20fever%20virus.jpg

  · Type species of the genus flavivirus

    · Tropical disease in Latin America and Africa

    · Transmitted through the bite of a female Aedes aegypti mosquito (the vector).

    · Incubation period: 3-6 days

    · Acute yellow fever—symptoms: Viremia, headache, malaise, nausea, muscle ache, flushing of head and neck, conjuntival infection, strawberry tongue.

    · Remission after acute yellow fever manifests as severe yellow fever—symptoms: fever, vomiting, abdominal pain, prostration.

    · Symptoms progress to involve the liver, kidneys and heart: e.g. jaundice.

http://lh4.ggpht.com/_YmfDLUdaIGU/SAFuz7jrw_I/AAAAAAAAAVM/4MOT98vdgxQ/Strawberry+tongue+%28Kawasaki+or+Scarlet+fever%29.jpg

Strawberry Tongue

Control of Yellow Fever Virus

    · Mosquito control (similar to dengue)

    · Immunnization with the vaccine containing live, attenuated yellow fever virus. Travelers to and residents of endemic areas should be immunized.

    · Protection lasts for up to 10 years; booster shots to be taken after that.

    · Because it is a live vaccine, it should not be given to immunocompromised people or to pregnant women.

West Nile Virus

  · Originated in Uganda

· Discovered in 1937

Symptoms

    · Usually mild to no symptoms

o Fever

o Headache, body aches

o Skin rash

o Swollen lymph glands

    · Severe Symptoms (occurring mainly in persons above 50 years old)

o Crossing blood-brain-barrier

o Encephalitis

o Meningitis

Transmission

    · Wild birds are the main reservoir of this virus

    · Vector is the mosquito, especially the Culex species

    · Humans are dead-end hosts

http://www.cdc.gov/ncidod/dvbid/westnile/misc/slides/komar/images/wnv-transmission-cycle.jpg

West Nile Virus Transmission Cycle

Control

    · No vaccine is available for west nile virus

    · Mosquito control

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