Ebola

Question 1

Why should we study EVD?

Answer 1

Current outbreak = most serious, largest and complex
Reported outside Africa
EVD infects wide range of cells
Mortality rate could be ~90%
EVD lacks specific treatments but vaccine trial

Question 2

What is EVD?

Answer 2

RNA filovirus

Ebola genus has 5 strains

Question 3

What are the 5 strains of EVD?

Answer 3

Sudan, Zaire, Tai Forest, Bundibugyo & Reston

Question 4

Who can be effected by EVD?

Answer 4

Humans/no human primates (monkeys/chimpanzees)

Question 5

What’s the average EVD case fatality rate?

Answer 5

Around 50%

Varied from 25% to 90% in past outbreaks

Question 6

When was the Ebola virus first recognised?

Answer 6

Two outbreaks occurred in Zaire & Sudan in 1976
284 people infected with a mortality rate of 53% (Sudan)
Zaire emerged = 318 people infected and 88% mortality rate

Question 7

What strain is the current outbreak?

Answer 7

Zaire

Question 8

Where did the current outbreak originate from?

Answer 8

Guinea then spread to Sierra Leone, Liberia, Nigeria, Senegal

Question 9

How many people were infected in the U.K. & USA?

Answer 9

UK = 3
USA = 11

Question 10

What’s the reservoir host of the Ebola Virus?

Answer 10

Evidence strongly suggests that bats are the reservoir host to Ebola virus.

Question 11

How is EVD transmitted?

Answer 11

Saliva
Contaminated surfaces
Blood
Sexual contact
Mother to foetus 
(Semen and possibly breast milk may be infectious in survivors for 7 weeks)

Question 12

What is the structure of Ebola?

Answer 12

RNA genome
Glycoproteins on surface- manufactured in ER and golgi
Viral envelope
800-1000 nm long
Nucleoprotein- virus proteins (NP, VP35 and polymerase) attached to piece of RNA
Matrix- VP40 and VP24 proteins.

Question 13

What are the functions of the proteins in Ebola Virus?

Answer 13

VP35- determines RNA to make proteins.
VP30- RT
VP40- Virus assembly and budding at the plasma membrane of infected cells

Question 14

Describe the Ebola genome

Answer 14

19kb and encodes 7 genes with 8 proteins

Question 15

What is targeted by EVD?

Answer 15

(Connective tissue)
Most immune cells (except. Lymphocytes)
Cells lining...
Liver 
Kidney
Lungs 
Blood vessel cells

Question 16

Describe the mechanism of infection 1-4

Answer 16

1) binds to receptors on cell
2) virus internalised into a macropinosome
3) trafficked into endosome containing proteases.
4) fusion- proteases digest GP which is triggered to initiate

Question 17

Describe the mechanism of infection for 5-8

Answer 17

5) replication- nucleocapsid released into cytoplasm where genome is replicated
6) transcription- with aid of the viral proteins VP35, 30 and L
7) translation- viral mRNAs translated
8) GP modification- brought to ER for mod.

Question 18

Describe the mechanism of infection for 9-11

Answer 18

9) GO modified in Golgi also and delivered to plasma mem. In secretory vesicles.
10) viral assembly- VP assemble with mem. Associated proteins (VP24, 40 and GP)
11) secretion/budding

Question 19

What is the pathology of EVD?

Answer 19

Viral replication triggers inflammatory chemical signals and leads to septic state.
Macrophages are the first cells infected with virus
Carry virus to nearby lymph nodes
Can enter bloodstream and lymphatic system

Question 20

What’s the incubation period of EVD?

Answer 20

2-21 days (humans not infectious until they develop symptoms)

Question 21

What are the symptoms of EVD infection?

Answer 21

Fever, fatigue, muscle pain, headache, sore throats, vomiting, diarrhoea, rash, impaired kidney function and liver function, internal and external bleeding, low WBCs and platelets, elevated liver enzymes.

Question 22

How is EVD diagnosed?

Answer 22

ELISA- Antigen capture detection tests, serum neutralisation test. Measures antibodies in blood
RT-PCR assay
Electron microscopy
Virus isolation by cell culture

Question 23

What’s sandwich ELISA (indirect)?

Answer 23

Antibody coated well- wash - add Antigen to be measured- wash- add enzyme - wash - add substrate and measure colour

Question 24

What’s a rapid diagnostic test for EVD?

Answer 24

eZyscreen <15 mins
Drop of blood, plasma or urine
ReEBOV p

Question 25

What are the treatments of EVD?

Answer 25

No effective treatment or vaccine 
Treat symptoms:
Maintenance of fluid and electrolyte balance 
Maintenance of O2 and BP
Barrier nursing
Isolation

Question 26

What’s Phase l of clinical trial?

Answer 26

Test new drug in small group of people, evaluate safety and determine safe dosage and identify side effects.

Question 27

What’s phase ll of clinical trial?

Answer 27

Larger group of people to see if effective and further evaluate safety.

Question 28

What’s phase lll?

Answer 28

Large groups to confirm effectiveness, monitor side effects, compare to commonly used treatments, collect info

Question 29

What’s phase lV?

Answer 29

Done after drug or treatment has been marketed to gather info in effect in various populations

Question 30

What’s STRIVE?

Answer 30

Potential vaccine for Ebola
Genetically engineering a weakened form of VSV virus so impersonates Zaire.
Snip out RNA that codes for GP that attach to human cell.
Remove RNA that codes for VSVs and replace with Ebola GP.
Tricks immune system into mounting response against Ebola