Ebola Flashcards
Why should we study EVD?
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
What is EVD?
RNA filovirus
Ebola genus has 5 strains
What are the 5 strains of EVD?
Sudan, Zaire, Tai Forest, Bundibugyo & Reston
Who can be effected by EVD?
Humans/no human primates (monkeys/chimpanzees)
What’s the average EVD case fatality rate?
Around 50%
Varied from 25% to 90% in past outbreaks
When was the Ebola virus first recognised?
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
What strain is the current outbreak?
Zaire
Where did the current outbreak originate from?
Guinea then spread to Sierra Leone, Liberia, Nigeria, Senegal
How many people were infected in the U.K. & USA?
UK = 3 USA = 11
What’s the reservoir host of the Ebola Virus?
Evidence strongly suggests that bats are the reservoir host to Ebola virus.
How is EVD transmitted?
Saliva Contaminated surfaces Blood Sexual contact Mother to foetus (Semen and possibly breast milk may be infectious in survivors for 7 weeks)
What is the structure of Ebola?
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.
What are the functions of the proteins in Ebola Virus?
VP35- determines RNA to make proteins.
VP30- RT
VP40- Virus assembly and budding at the plasma membrane of infected cells
Describe the Ebola genome
19kb and encodes 7 genes with 8 proteins
What is targeted by EVD?
(Connective tissue) Most immune cells (except. Lymphocytes) Cells lining... Liver Kidney Lungs Blood vessel cells
Describe the mechanism of infection 1-4
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
Describe the mechanism of infection for 5-8
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.
Describe the mechanism of infection for 9-11
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
What is the pathology of EVD?
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
What’s the incubation period of EVD?
2-21 days (humans not infectious until they develop symptoms)
What are the symptoms of EVD infection?
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.
How is EVD diagnosed?
ELISA- Antigen capture detection tests, serum neutralisation test. Measures antibodies in blood
RT-PCR assay
Electron microscopy
Virus isolation by cell culture
What’s sandwich ELISA (indirect)?
Antibody coated well- wash - add Antigen to be measured- wash- add enzyme - wash - add substrate and measure colour
What’s a rapid diagnostic test for EVD?
eZyscreen <15 mins
Drop of blood, plasma or urine
ReEBOV p
What are the treatments of EVD?
No effective treatment or vaccine Treat symptoms: Maintenance of fluid and electrolyte balance Maintenance of O2 and BP Barrier nursing Isolation
What’s Phase l of clinical trial?
Test new drug in small group of people, evaluate safety and determine safe dosage and identify side effects.
What’s phase ll of clinical trial?
Larger group of people to see if effective and further evaluate safety.
What’s phase lll?
Large groups to confirm effectiveness, monitor side effects, compare to commonly used treatments, collect info
What’s phase lV?
Done after drug or treatment has been marketed to gather info in effect in various populations
What’s STRIVE?
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
