Flaviviruses

Question 1

Genome type

Answer 1

(+)ssRNA

Question 2

Capsid structure

Answer 2

Icosahedral

Question 3

Enveloped?

Answer 3

Enveloped

Question 4

VAP and does it do fusion?

Answer 4

Envelope (E) protein which also has fusion activity

Question 5

E protein

Answer 5

VAP, fusion activity, antiparallel homodimers forms icosahedral-like structure around the capsid

Question 6

C protein

Answer 6

Capsid, forms true icosahedron

Question 7

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.

Answer 7

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

Question 8

M protein

Answer 8

Matrix protein, connects E and C proteins

Question 9

What mainly transmits them?

Answer 9

arthropod secondary vectors (ticks and mosquitos)

Question 10

Host receptors (Just know one)

Answer 10

TIM

Question 11

How does it enter the cell?

Answer 11

Receptor mediated endocytosis
Antibody mediated endocytosis

Question 12

Is fusion involved and if it is is it pH dependent?

Answer 12

Acidification caused fusion and the virus leaves the endosome

Question 13

Where is it replicated in the cell?

Answer 13

In the cytosol

Question 14

What serves as the flavivirus mRNA transcript?

Answer 14

A single Open Reading Frame is translated into one polyprotein that integrates into the ER membrane

Question 15

How are discrete, individual proteins made?

Answer 15

Viral and host proteases cleave it into 10 proteins

Question 16

Where is the polyprotein processed?

Answer 16

ER

Question 17

Where is it assembled?

Answer 17

ER

Question 18

What happens after assembly?

Answer 18

It moved through the golgi and the acidification turns it from rough to smooth

Question 19

How does pH affect the maturation state of flaviviruses?

Answer 19

Low pH = smooth = mature

High pH = rough

Question 20

Furin

Answer 20

Cleaves pr to make the virus permanently smooth (and mature)

Question 21

How many proteins are translated?

Answer 21

A single ORF is translated into a giant polyprotein which integrates into the ER membrane

Question 22

How many final proteins are there?

Answer 22

The polyprotein is cleaved by virus and host proteases into 10 functional proteins

Question 23

What is “breathing”

Answer 23

The process of particles going from spiky to smooth and back depending on pH (low = smooth) and temperature

Question 24

Example viruses

Answer 24

Yellow fever
Dengue fever
West Nile
Zika

Question 25

Yellow fever primarily replicates in what ecosystem

Answer 25

African and South America in the jungle (sylvatic) cycle with mosquitoes and nonhuman primates

Question 26

How is fellow fever sustained in the city

Answer 26

Humans and mosquitoes

Question 27

Yellow fever Pathogenesis

Answer 27

1. Mosquito feeds and innate cells are recruited 2. Virus infects local immune cells (dendritic) 3. Dendritic cells go lymph nodes and activate adaptive 4. Viremia spreads virus to organs 5. Secondary replication in liver and cause severe liver damage

Question 28

Primary site of replication for yellow fever

Answer 28

Local dendritic cells

Question 29

Secondary site of infection for yellow fever

Answer 29

Hepatocytes

Question 30

Primary site of infection for dengue fever

Answer 30

Innate immune cells (dendritic, mast, macrophages)

Question 31

Secondary sites of infection for dengue fever

Answer 31

Liver and spleen

Question 32

Antibody dependent enhancement

Answer 32

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

Question 33

Dengue fever transmission

Answer 33

Aedes aegypti or albopictus mosquitoes Mother to fetus

Question 34

West Nile transmission

Answer 34

Mosquitoes spread to birds and vice versa Mosquitoes also spread to horses and us

Question 35

Zika transmission

Answer 35

Most = mosquito to human Other = mother to fetus, sex, blood transfusion

Question 36

Why can both humans AND mosquitos be considered primary reservoirs for some flaviviruses?

Answer 36

All flaviviruses cause viremia which then causes the spread between human and mosquito/arthropod vectors and the virus replicates in BOTH of us

Question 37

Appreciate the impact ecological disturbances and climate change may have on flavivirus distribution (and why this is).

Answer 37

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