Ebola virus: how it is made and how it infects humans

The genusEbolais part of the Filovirus family (Filoviridae) and includes6 species of viruses. The first, discovered in 1976 in Africa, is called Zaireebolavirus (EBOV) because it was discovered in what is now called the Democratic Republic of Congo, but which was once called Zaire. The virus was discovered near theEbola River, hence its name. Of these six species only 3 have been responsible, so far, for large epidemics (in addition to Zaire ebolavirus, also Bundibugyo ebolavirus and Sudan ebolavirus).

The family name of the Ebola virus (Filovirus) comes from the Latin word “filum” and is given by the characteristicexternal filament shapeobserved through electron microscopy images. These viruses consist of a phospholipid pericapsid, the outermost envelope, similar to the human cell membrane. The pericapsid exposes some key proteins for infection to the outside. Inside there is a protein nucleocapsid that contains the genetic material that in this virus consistsof an RNA strand. On the outermost coating (the pericapsid) the virus possesses the GP protein that binds to the target cell receptor.

Once the binding has occurred, the cell lets it enter through the fusion of membranes (viral and cellular). The fusion of the membranes forms a vesicle that allows the entry of the nuclecapsid containing the viral RNA into the cell.

How single stranded negative RNA viruses replicate

Ebolavirusesaresingle-stranded negative RNA viruses. Their RNA is complementary to the true sequence of the virus and does not constitute the sequence itself. This means that, once inside the host cell, the virus cannot translate its RNA into viral proteins, but must first transcribe it into a positive sequence mRNA. To do this it needs a protein complex, RNA-dependent RNA polymerase, which is contained within the viral particle, in the nucleocapsid.

Once the negative RNA has been transcribed into the positive one it can be translated normally producing all the components of the virus: the proteins (including those of the nucleocapsid and pericapsid) and also the RNA polymerase mentioned above. The RNA of the virus is replicated from mRNA positive (and then negative again). In this way, everything necessary is produced to assemble new viral particles identical to the original that can leave the host cell to infect others.

Epidemiology

Ebola viruseshave been discovered in Africa and epidemics, in the past, have remained quite contained because they occurred in rather isolated and rural areas.

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The fatality rate in this case was 59% and it involved thousands of people.

Contagion and transmission of the Ebola virus

Like all viruses, Ebola is unable to replicate and complete its cycle without the help of a host cell to infect. In fact, he needs the cell to supply the essential elements it does not have and that is why he is forced to infect it.

The target of Ebolaviruses are endothelial cells, hepatocytes and mononuclear phagocytes.

• infected animals, alive or dead (monkeys, chimpanzees, gorillas, antelopes, porcupines and fruit bats);
• infected humans, dead or alive;
• infected blood, organs or secretions with mucous membranes or wounds of healthy individuals;

Contagion can also occur indirectly through contact with environments contaminated by these infected fluids. In the rare cases of survivors, it has been seen that they are able to infect through semen even several weeks after complete recovery.

Ebola virus disease symptoms

Symptoms of Ebola virus disease begin soon after incubation ranging from 2 to 21 days and are:

• Fever
• severe exhaustion,
• joint pain,
• muscle aches,
• headache.

Later the exhaustion becomes severe asthenia, diarrhea appears with bleeding, nausea, vomiting and anorexia.

Subsequently there is a reduction of hepatic, gastrointestinal, renal, respiratory functions, skin, vascular and central nervous system damage are highlighted.

As the disease progresses, severe internal and external bleeding, tachypnea, hypovolemic shock, multi-organ failure syndrome, and eventually death occur. Not all of these symptoms appear in all patients, but many of them do.

Diagnosis

In the first days after infection, it is very difficult to diagnose EVD diseasedue to the non-specificity of the first symptoms encountered. For this reason and for the fact that it is essential to diagnose it very early avoiding other infections, we proceed by evaluating the symptoms also on the basis of the place where we are when the infection occurs and the epidemic factor of their appearance. So, to give an example, these same symptoms turn on alarm bells in health personnel in Africa rather than in Europe.

In any case, immediate isolation and Communication of the Case to International Health Authorities is essential for any suspected case .

Once the suspicion arises, in the first phase of the disease we proceed with two laboratory analyzes that identify the virus in the patient:

• ELISA test to detect viral antigens
• PCR analysis to identify the viral genome

In the next, and more serious, phase of the disease, antibodies against the virus in the patient’s blood, which were previously absent ( serological test ), can be searched for.

Treatment and vaccine

In December 2019 FDA approved the experimental Ebola vaccine , called rVSV-ZEBOV (trade name Ervebo ^®) , which gave a very good response against the Zaire ebolavirus (in a 2015 study, no cases of Ebola among the 5837 people vaccinated against the 23 cases that occurred among the unvaccinated over the following weeks).

Ervebo ^® is a recombinant vaccine in which live and attenuated vesicular stomatitis virus has been modified to contain the EBOV glycoprotein gene from Zaire Ebola virustags. By leading to the synthesis of only one glycoprotein of the Ebola virus, vaccination cannot cause disease. Administered as a single-dose vaccine, it was found to be safe and protective against Zaire ebolavirus (it does not provide protection against otherEbolavirus  or  Marburgvirus species).

In the event of contagion, to date there is no cure (possible pharmacological and immune therapies are also being evaluated) and currently an attempt is made to keep the patient alive for as long as possible until the rare recovery implemented by the immune defenses.

To keep patients alive, we proceed with intravenous and oral rehydrationand with the treatment of symptoms as they appear. Thelife expectancy of a patient in Africa is therefore not the same as that of a patient in more developed countries, precisely because of the different availability of equipment and products, but in all cases they are probabilistically very low.

Prevention

Since the origin of the virus has not been precisely found, it is not possible to intervene in this sense at the source and the only prevention consists in Early diagnosis and in the strict isolation of the positives .

The virus is not inactivated by freezing and survives for a few days in liquid or dry materials outside the body.