Ebola Flashcards
Describe the structure of Ebola
6
Pleiomorphic Filamentous Striated 80nm diameter 130-140000 nm long Enveloped (lipid, protein coat derived from host cell membrane)
Genome
4
19kb negative sense ssRNA
Unsegmented (no opportunity for reassortment)
Coding 7 proteins
Gene overlap (two or more proteins coded for by the same nucleotide sequence)
Name the Ebola Proteins
7
Gp-transmembrane glycoprotein Np-nucleoprotein necessary for capsid assembly Vp24-matrix protein ogligomers Vp30-initiator of transcription Vp35- inhibits IFN production Vp40- capsid assembly and budding L-viral polymerase
Describe Ebola replication cycle
5 with about 4 points per stage
1) host entry
-contact with infected bodily fluids from people or animals e.g. Fruit bats or primates
-enters through mucous membranes or via blood (needle stick)
-experimental infection via aerosol
2) absorption- gp1 binds cellular receptors
-Tim-1 expressed on human airway and eye epithelial cells
-phagocytic cells are primary target, but don’t express time-1, other receptors e.g. L-sign and Dc-sign
3)Endocytosis
-ph lowering in the endosome
-GPcl binds niemann-pick C1
-GP2 mediates release of viral particles into cytoplasm
4) protein synthesis
-requires viral polymerase
-VP30 anti-terminator allows transcription of genes downstream from first gene only
-vp35 prevents anti-viral responses to dsRNA
Gp synthesis
-complex post translational processing
-o-linked/n-linked glycosylation
-proteolytic cleaving by pro teases
-acylation
5)virus assembly and release
Describe Ebola glycoproteins
3
GP1/GP2- transmembrane protein involved in binding and fusion
Soluble GP- truncated soluble protein (unique to Ebola)
-secreted
-function Unknown, thought to be a decoy for immune system
-gives rise to neutralising and protective antibodies
Interactions with the immune system
- monocytes primary target (carry virus throughout body,lysis releases cytokines)
- early infection of dendritic cells( delays specific immune response)
- over expression of pro inflammatory signals (cytokines, does not clear infection)
- vp35 inhibition of IRF3 (no transcription of IFN genes, no antiviral response to dsRNA)
- inhibition/destruction of immune cells e.g. Neutrophils/macrophages
Pathogenesis
2
- GP responsible for cytopathic effects of virus (breakdown of extra cellular matrix, sGP inhibits neutrophils)
- evidence suggests virus doesn’t directly cause most of disease
What causes most of the disease?
3
- massive immune response
- activation of macrophages and monocytes (clumping may cause coagulation observed in some clinical cases)
- proinflammatory signals release ( cytokines,tnf-alpha break down endothelial barrier and blood leaks into tissue which causes shock and is the most frequent cause of death)
Describe the symptoms of Ebola
3
- abrupt onset:flu like symptoms
- rash,red eyes,internal/external bleeding
- Death 30-90%
Progression of the disease
3
2-21 day incubation
- Some people survive, larger immune response in those that do
- virus may remain for up to 3-9 months( convalescent human reservoir, virus present in seminal fluid)
Biological weapon who ?
2
1992 Russia
Japanese cult tried to obtain it
Why is it a good biological weapon
- no vaccine
- no treatment
- high infectivity ( as few as 17 particles)
- aerosol ideal
Name the three small molecule drugs whic one kinda works?
Amiodarone
Brincidofovir
Favipiravir- kinda works
Name the three biologicals and which one kinda works?
Convalescent plasma
Zmapp- kinda works
Tkm-ebola
What family is Ebola in and describe
4
Filoviridae
Filo- threadlike
Two genera- Marburg-like virus, Ebola like virus
Structurally and genetically similar to rhadoviridae and paramyxoviridae
