Flaviviruses Flashcards
Genome type
(+)ssRNA
Capsid structure
Icosahedral
Enveloped?
Enveloped
VAP and does it do fusion?
Envelope (E) protein which also has fusion activity
E protein
VAP, fusion activity, antiparallel homodimers forms icosahedral-like structure around the capsid
C protein
Capsid, forms true icosahedron
What do I mean when I state that the flavivirus lipid membrane is flanked by two icosahedral structures? Consider how this particle structure is advantageous in its transmission cycle.
The capsid (C) is a true icosahedron and the envelope (E) forms antiparallel dimers which assemble and are icosahedral-like
The E proteins protect the membrane
M protein
Matrix protein, connects E and C proteins
What mainly transmits them?
arthropod secondary vectors (ticks and mosquitos)
Host receptors (Just know one)
TIM
How does it enter the cell?
Receptor mediated endocytosis
Antibody mediated endocytosis
Is fusion involved and if it is is it pH dependent?
Acidification caused fusion and the virus leaves the endosome
Where is it replicated in the cell?
In the cytosol
What serves as the flavivirus mRNA transcript?
A single Open Reading Frame is translated into one polyprotein that integrates into the ER membrane
How are discrete, individual proteins made?
Viral and host proteases cleave it into 10 proteins
Where is the polyprotein processed?
ER
Where is it assembled?
ER
What happens after assembly?
It moved through the golgi and the acidification turns it from rough to smooth
How does pH affect the maturation state of flaviviruses?
Low pH = smooth = mature
High pH = rough
Furin
Cleaves pr to make the virus permanently smooth (and mature)
How many proteins are translated?
A single ORF is translated into a giant polyprotein which integrates into the ER membrane
How many final proteins are there?
The polyprotein is cleaved by virus and host proteases into 10 functional proteins
What is “breathing”
The process of particles going from spiky to smooth and back depending on pH (low = smooth) and temperature
Example viruses
Yellow fever
Dengue fever
West Nile
Zika
Yellow fever primarily replicates in what ecosystem
African and South America in the jungle (sylvatic) cycle with mosquitoes and nonhuman primates
How is fellow fever sustained in the city
Humans and mosquitoes
Yellow fever Pathogenesis
- Mosquito feeds and innate cells are recruited
- Virus infects local immune cells (dendritic)
- Dendritic cells go lymph nodes and activate adaptive
- Viremia spreads virus to organs
- Secondary replication in liver and cause severe liver damage
Primary site of replication for yellow fever
Local dendritic cells
Secondary site of infection for yellow fever
Hepatocytes
Primary site of infection for dengue fever
Innate immune cells (dendritic, mast, macrophages)
Secondary sites of infection for dengue fever
Liver and spleen
Antibody dependent enhancement
Prior infection with one serotype creates antibodies that ENHANCE infection of other serotypes
New serotype is NOT NEUTRALIZED by old antibodies and is internalized in monocyte and replicates in it
Dengue fever transmission
Aedes aegypti or albopictus mosquitoes
Mother to fetus
West Nile transmission
Mosquitoes spread to birds and vice versa
Mosquitoes also spread to horses and us
Zika transmission
Most = mosquito to human
Other = mother to fetus, sex, blood transfusion
Why can both humans AND mosquitos be considered primary reservoirs for some flaviviruses?
All flaviviruses cause viremia which then causes the spread between human and mosquito/arthropod vectors and the virus replicates in BOTH of us
Appreciate the impact ecological disturbances and climate change may have on flavivirus distribution (and why this is).
We are encroaching on the jungle (sylvatic cycle) and are exposed to more non human primates and infected mosquitos from them
Warmer temps allow mosquitos to travel to new places and take longer to freeze to death
