B4 - Ebola virus

Ebola is highly pleomorphic. What does this mean?

It can adapt different shapes. Doesn’t have a rigid structure like some other viruses.

What are the six subtypes of Ebola?

• Zaire

• Bundibugyo

• Sudan

• Tai forest

• Reston

• Bombali

How is Ebola transmitted?

Via contact with bodily fluids of infected persons or animals.

What are some symptoms of ebola?

• Non-specific flu like symptoms

• Diarrhoea and vomiting

• Maculopapular rash in 50% of people

• Severe bleeding (particularly GI bleeding)

• Death due to multi organ failure

What are two recommended Ebola therapies?

mAb114 (Ebanga)

REGN-EB3 (Immazeb)

What are two monoclonal antibody therapies which are no longer recommended for Ebola?

Remdesivir (Veklury)

ZMapp

Vaccination for Ebola is only against one particular strain. What is that strain?

Zaire strain of Ebola.

When is the Ebola vaccine Ervebo used?

Used during outbreaks

Individuals around the infected are vaccinated to try and prevent its spread without needing to vaccinate everyone

When are the Ebola vaccines, Zabdeno and Mvabea, used?

Used before outbreaks as a prophylactic.

Mass vaccination of the whole population.

What is thought to be the primary reservoir of Ebola?

Fruit bats (which are asymptomatic when infected)

However, the virus can also spread via dead chimpanzees, gorillas and antelopes despite them not being the reservoir

What shape of virus is Ebola?

Enveloped helical virus

What type of genome does Ebola have?

Negative sense single stranded RNA genome

The L-protein of Ebola is used for what?

The L-protein is the viruses RdRp which is used for RNA replication

How can Ebola be safely studied without the risk of handling live Ebola viruses?

VSV-Ebola pseudotype viruses can be used.

These viruses are modified Vesicular stomatitis virus which has had it’s glycoprotein gene replaced with green fluorescent protein gene.

The virus is combined with Ebola virus glycoproteins which allows it to infect target cells.

• However, since the glycoprotein gene has been replaced, the virus cannot produce infectious virus particles.

Ebola is pantropic. What does this mean?

It is capable of infecting many cell types and is not specific to a particular cell.

What cell does Ebola initially infect?

Monocytes, dendritic cells and macrophages.

Later infects, epithelial cells.

What receptor does Ebola bind to on Macrophages/Dendritic cells?

DC-SIGN

What receptor does Ebola bind to on macrophages/neutrophils?

TREM

What receptor does Ebola bind to on hepatocytes?

Asialoglycoprotein

How does Ebola cause defects in coagulation mechanisms?

Can cause an increase in expression of tissue factor on macrophages and endothelial cells which activates coagulation.

This can block flow to major organs if coagulation occurs in capillaries.

This can also ‘mop up’ platelets and coagulation factors which prevents them from being used for normal bleeding.

How does Ebola suppress the immune system?

• Suppresses production and action of IFNa and IFNb

• Supresses activation of T/B-cells

• Depletes lymphocytes and NK cells

What is the mechanism of Ebola suppression of IFN?

VP35 protein inhibits IRF3 production which prevents IFNa and IFNb production.

VP24 inhibits nuclear accumulation of tyrosine phosphorylated STAT1 which prevents IFN signalling

What type of response occurs in a lethal Ebola infection?

• No CD8+ T-cell activation

• Below-normal numbers of T-cells

• No detectable antibodies in blood

• High Nitric Oxide (NO)

What type of response occurs in a non-lethal Ebola infection?

• Prominent CD8+ T-cell activation

• Above-normal numbers of T-cells

• Detectable antibodies in blood

• Low Nitric Oxide (NO)