What is Ebola virus, where does it come from?

Submitted by AWL on 7 October, 2014 - 6:19 Author: Les Hearn

From a scary but rare problem, Ebola Virus has exploded into public consciousness as a real disaster in West Africa and a potential threat to anywhere else connected by any means of travel.

The problem has been exacerbated by the lack of local health care infrastructure, distrust of aid agencies and lack of help from the richest countries. Where has the virus come from and why is it now such a problem?

Back in 1976, a new virus was discovered in a group of villages in the equatorial forests of Zaire (now Democratic Republic of Congo). Victims suffered fever, pain, vomiting, diarrhoea, and massive internal bleeding (haemorrhage): 70% died.

A young Belgian microbiologist, Peter Piot,* examined blood samples from an affected woman, a nun from a mission, and found large worm-shaped viruses of an unknown kind. It was similar to Marburg virus (discovered 1967), which also caused a haemorrhagic fever with high mortality. They were both members of the Filoviridae family of the order Mononegavirales, most of which cause serious plant and animal diseases.

Piot went with a team to Zaire to find an epidemic that was out of control. To stop it, they needed to know how the virus was spread. Mapping the distribution of cases implicated the local hospital: the fact that many victims were women who had attended the antenatal clinic was even more suspicious. It turned out that they had received routine injections but with re-used needles: the virus thus spread in blood or body fluids. Other cases were among attenders at funerals who had taken part in washing or preparing bodies for burial.

Stopping transmission of the virus was simply a matter of quarantining cases, closing the hospital, and informing people of the need to avoid touching victims’ bodies. Piot’s team was near River Ebola, hence the name Ebola Virus.

But where had the virus come from? Obviously not the hospital. It was likely that the normal host was a forest-dwelling animal not greatly, if at all, affected by it. In fact, it seems to be carried by fruit bats which are eaten as a type of “bush meat”. It’s also found in gorillas and perhaps other animals eaten as bush meat. These healthy carriers would not carry great numbers of virus so transmission to humans would normally be rare.

Outbreaks are in fact rare, with many years free of cases. Up to this year, the average number of cases reported per year has been 63, with a mortality of two-thirds. Outbreaks have become more frequent since 2000 but the average has still been well under a hundred with a mortality of three-fifths (perhaps reflecting an improvement in supportive care).

The recent outbreaks in Guinea, Sierra Leone and Liberia have affected over 6500 people, 100 times the average of all previous outbreaks and more than ten times the previous worst. The reasons for this are not clear. Population growth, with greater overcrowding, has been suggested as a factor, as has increased consumption of bush meat, but these cannot have been much different during the previous six years when there were 32, 1, 0, 0, 88, and 0 cases, respectively.

Victims should be isolated and contacts traced.** This is difficult when people flee affected areas. Hygienic practice should be enforced and funeral practices modified to avoid contact with virus-laden bodies. A large number of cases have been among healthcare staff who need to take special precautions to avoid contact. Researchers have to wear pressure suits to avoid any chance of touching or inhaling virus particles: these are expensive and not widely available in West Africa. Surfaces and instruments need to be sterilised and it should go without saying that needles must not be re-used. Unfortunately, these precautions are difficult to take in remote areas or in countries with poor health services.

Viruses are not affected by antibiotics so most treatment is palliative or supportive (pain management, anti-nausea drugs, rehydration).

Early rehydration may reduce mortality. In a positive example of military intervention, US and UK armed forces are setting up field hospitals in Liberia and Sierra Leone, with France doing the same in Guinea. In the first instance, they will concentrate on treating medical personnel.

The ideal would be a vaccine and safety tests on candidate vaccines using healthy volunteers have been accelerated. This will not prove that they work since it would be unethical to try to infect volunteers with Ebola Virus. However, animal tests are promising.

The theory is that they would stimulate the immune system to produce antibodies that would stick to the virus particles and prevent them infecting more cells. Vaccines have been outstandingly successful, most notably against smallpox which no longer exists.

The experimental antibody treatment ZMapp has been given to Western medical workers and some African doctors, most of whom survived. Unfortunately, supplies of ZMapp have run out. It is not clear that it works in humans though it is very successful in monkey tests. The theory is that the antibodies, produced in large amounts by immune system cells extracted from mice infected with Ebola virus, will stick to virus particles in the blood, preventing them from infecting more cells. This supplements the victim’s immune response to the virus.

Another suggestion is to extract natural antibodies from the blood of survivors (who presumably had a good immune response to the infection) and inject them into other victims. It is not clear that this would supply anything like enough antibody.

A further development is TKM-Ebola which contains “small interfering RNAs”. These are complementary strands of RNA that would bind to some of the genes on the virus’s RNA genome, preventing them from being translated into proteins. This would prevent new virus particles being formed. It is not clear if it would work but it is certainly worth a try!

Notes

* Peter Piot was inspired to go on studying diseases in Africa, researching the AIDS epidemic and later becoming the first executive director of UNAIDS. He is Professor of Global Health at the London School of Hygiene and Tropical Medicine. He has recently become involved in the Longitude Project, looking for solutions to the problem of drug-resistant microbes.

** The recent case in Dallas, Texas, appears to have been completely mishandled. Thomas Duncan had just arrived from Liberia and went to hospital when he felt unwell. They failed to realise the significance of these facts and sent him home with antibiotics (for what they thought was a virus infection!?). Two days later, he was taken back to hospital in a serious condition, having potentially infected his family and the ambulance staff. You couldn’t make it up!

What do viruses do?

Viruses have a rather sneaky way of behaving which makes them very difficult to combat.

They consist of a genome (instructions for making a new virus) and a protein coat that helps them invade cells which can be plant, animal, fungi or bacteria. They do not contain the other components necessary for life so are often not considered to be be living in the normal sense. Instead, they hijack the host cell’s life support system and use it to reproduce.

Their genomes can be made of double-stranded DNA shaped like a spiral ladder (the double helix), like that of every type of ordinary cell, single-stranded DNA (which still contains all the information needed), double-stranded RNA (a related compound) or single-stranded RNA.

DNA genomes can be used straightaway to make messenger RNA for each gene, then to make protein using the host cell’s protein-making apparatus. The genome is copied and the coat proteins wrap themselves round this, making lots of new virus particles to be released, killing the host cell.

RNA retroviruses transcribe their RNA into DNA which is then incorporated into the host cell DNA. Then it carries on as for DNA viruses, making more virus particles.

The Filoviridae (worm-shaped viruses including Ebola, Marburg) and their relatives in the Mononegavirales (including ‘flu, mumps, rabies, distemper, and measles), with a single strand of RNA, form a matching strand of RNA which is then used to make proteins, as well as copies of the original RNA strand. New virus particles are formed and released. This kills the host white blood cells (harming the immune system), liver cells (causing liver damage), and endothelial cells, which line blood vessels and other tubules (explaining the bleeding that occurs in later stages).

One of the most fascinating discoveries from the human genome studies is that about 8% of our DNA is of viral origin in the form of endogenous viral elements (EVEs). Many of these are the remains of retroviral DNA that mutated and couldn’t replicate any more. Smaller amounts come from many other types of virus, including ancient Filoviridae. It’s not clear how this happened but happen it did, probably some 40 million years ago. For these viral fossils to have survived, it may be that they confer some protection from filoviruses.

Most of these EVEs probably do no harm or good, though some may predispose to cancer. However, there is one viral “fossil” that is a functional gene and plays a crucial role in mammals with a placenta. It produces a protein, syncytin, which originally made host cells fuse with each other, helping viruses spread. In placental mammals, it makes the placenta fuse with the uterus, allowing the foetus to gain more nutrients from the mother and become much more mature before being born. By contrast, in marsupials, the young are born tiny and very immature, while monotremes lay eggs.

A very exciting theory (but just a theory) is that the nuclei of protozoa, animals, plants and fungi are descended from a giant virus that took over an ancestral bacterial cell and never left. Its genome would have captured genes from the host cell, becoming the main store of hereditary DNA.

Giant viruses exist now and have some similarities to the nucleus, including a double membrane and linear DNA, unlike the circular bacterial DNA molecule.