Genetic evolution: how the Ebola virus changes and adapts

As viruses replicate, their genome changes. Image: EPA/Ahmed Jallanzo

As viruses replicate, their genome changes. Image: EPA/Ahmed Jallanzo

By Glenn Marsh, CSIRO

The current outbreak of Ebola virus in West Africa is unprecedented in size, with nearly 4,800 confirmed or probable cases and more than 2,400 deaths. People have been infected in Guinea, Liberia, Sierra Leone, Nigeria and Senegal.

The World Health Organization declared this outbreak a “public health emergency of international concern” in August and estimates it will claim a staggering 20,000 lives within the next six months.

A second completely independent and significantly smaller Ebola virus outbreak has been detected in the Democratic Republic of the Congo.

Like all viruses, the Ebola virus has evolved since the outbreak began. So, how does this occur and how does it impact our attempts to contain the disease?

Tracking Ebola

Ebolavirus and the closely related Marburgvirus genera belong to the Filoviridae family. Both of these genera contain viruses that may cause fatal haemorrhagic fevers.

The Ebola virus genus is made up of five virus species: Zaire ebolavirus (responsible for both of the current outbreaks), Sudan ebolavirus, Reston ebolavirus, Bundibugyo ebolavirus and Taï Forest ebolavirus.

In order to better understand the origin and transmission of the current outbreak in West Africa, researchers from the Broad Institute and Harvard University, in collaboration with the Sierra Leone Ministry of Health, sequenced 99 virus genomes from 78 patients.

The study, reported in Science, shows the outbreak resulted from a single introduction of virus into the human population and then ongoing human-to-human transmission. The scientists reported more than 300 unique changes within the virus causing the current West African outbreak, which differentiates this outbreak strain from previous strains.

The current Ebola outbreak has infected nearly 5,000 people. Image: EPA/Ahmed Jallanzo

Within the 99 genomes sequenced from this outbreak, researchers have recorded approximately 50 other changes to the virus as it spreads from person to person. Future work will investigate whether these differences are contributing to the severity of the current outbreak.

These 99 genome sequences have been promptly released to publicly available sequence databases such as Genbank, allowing scientists globally to investigate changes in these viruses. This is critical in assessing whether the current molecular diagnostic tests can detect these strains and whether experimental therapies can effectively treat the circulating strains.

How does Ebola evolve?

This is the first Ebola virus outbreak where scientists have sequenced viruses from a significant number of patients. Despite this, the Broad Institute/Harvard University study findings are not unexpected.

The Ebola virus genome is made up of RNA and the virus polymerase protein that does not have an error-correction mechanism. This is where it gets a little complicated, but bear with me.

As the virus replicates, it is expected that the virus genome will change. This natural change of virus genomes over time is why influenza virus vaccines must be updated annually and why HIV mutates to become resistant to antiretroviral drugs.

Changes are also expected when a virus crosses from one species to another. In the case of Ebola virus, bats are considered to be the natural host, referred to as the “reservoir host”. The virus in bats will have evolved over time to be an optimal sequence for bats.

Knowing how the Ebola virus adapts will help health officials contain future outbreaks. Image: EPA/Ahmed Jallanzo

Crossing over into another species, in this case people, puts pressure on the virus to evolve. This evolution can lead to “errors” or changes within the virus which may make the new host sicker.

Ebola viruses are known to rapidly evolve in new hosts, as we’ve seen in the adaptation of lab-based Ebola viruses to guinea pigs and mice. This adaptation occurred by passing a low-pathogenic virus from one animal to the next until the Ebola virus was able to induce a fatal disease. Only a small number of changes were required in both cases for this to occur.

While this kind of viral mutation is well known with other viruses, such as influenza virus, we are only truly appreciating the extent of it with the Ebola viruses.

What do the genetic changes mean?

The Broad Institute/Harvard University study reported that the number of changes in genome sequences from this current outbreak was two-fold higher than in previous outbreaks.

This could be due to the increased number of sequences obtained over a period of several months, and the fact that the virus has undergone many person-to-person passes in this time.

However, it will be important to determine if virus samples from early and late in the outbreak have differing ability to cause disease or transmit. The genetic changes may, for example, influence the level of infectious virus in bodily fluids, which would make the virus easier to spread.

Analysing this data will help us understand why this outbreak has spread so rapidly with devastating consequences and, importantly, how we can better contain and manage future outbreaks.

Glenn Marsh receives funding from Australian National Health and Medical Research Council and Rural Industries Research and Development Corporation.

This article was originally published on The Conversation.
Read the original article.


Ebola outbreak causes global concern

Ebola virus

An electron microscope image of Ebola virus

The World Health Organization has confirmed the current outbreak of Ebola virus in Africa is the largest recorded outbreak, killing 672 of the 1201 confirmed cases since February this year.

So it’s no surprise that there’s increasing global concern about the spread of this virus – the situation is undeniably scary. Here’s what you need to know.

What is Ebola virus?

Ebola virus, also known as Ebola hemorrhagic fever, is a highly infectious illness with a fatality rate of up to 90 per cent. The virus is feared for its rapid and aggressive nature. Symptoms initially include a sudden fever as well as joint and muscle aches and then typically progress to vomiting, diarrhoea and, in some cases, internal and external bleeding. Contrary to Hollywood’s depictions, many people do not suffer massive and dramatic blood loss. They instead die from the shutdown of vital organs like the liver and kidneys.

Prior to this current situation, the largest outbreak of Ebola virus involved 425 people in Uganda, in 2000.

Ebola virus is a zoonotic disease – one that passes from animals to people. As with the respiratory diseases SARS and Hendra virus, bats have been identified as the natural host.  There is good evidence to suggest other mammals like gorillas, chimpanzees and antelopes are most likely the transmission host to people but the way the infection passes to them from the fruit bats is still not clear.

Why is it called Ebola?

The virus was first discovered in 1976, with two simultaneous outbreaks of the disease – one near the Ebola River in Zaire (now the Democratic Republic of Congo), and the other in Nzara, Sudan. Since then more than 1600 deaths have been recorded.

How does the virus spread?

The virus is transmitted from wild animals to people. It can then spread through contact with bodily fluids from someone who is infected, or from exposure to objects like contaminated needles. People most at risk include health workers and family members or others who are in contact with the infected people.

Are there any treatments available?

There is no vaccine or known cure for Ebola virus infection. As with many emerging infectious diseases, treatment is limited to pain management and supportive therapies to counter symptoms like dehydration and lack of oxygen. Public awareness and infection control measures are vital to controlling the spread of disease.

What is CSIRO doing?

We have been researching the Reston ebolavirus strain, which is endemic in parts of Asia, for several years at the Australian Animal Health Laboratory (AAHL) as part of our mandate to study new and emerging infectious diseases to ensure we’re prepared should they ever reach Australia.

In 2013, following approval from the Australian government, we imported several Ebola virus isolates including the Zaire ebolavirus strain from Africa for research purposes.  We’re investigating the pathogenicity, or disease causing ability, of these viruses, to understand why the African strains have a high fatality rate in people, compared to the Asian strain, which does not cause human disease.

There are strict international protocols, government approvals and security measures in place to ensure such viruses are transported and imported safely.  At AAHL, all work with Ebola viruses is at the highest level of biocontainment, deep within the facility’s solid walls. Our specialist staff must work on the virus wearing fully encapsulated suits with their own external air supply.

Biosecurity level 4 spacesuit and scientist

CSIRO scientist Glenn Marsh working at the highest level of biosecurity

Although most of our research is in cell and tissue culture, in the coming weeks our scientists plan to work with ferrets, which have shown human-like responses to infection with other high-risk pathogens, to understand what makes the Ebola virus pathogenic. We believe that understanding the differences in virulence between the two closely related strains of Ebola may hold the key to developing an effective vaccine to prevent this deadly disease, or therapeutics to treat it.

Why is CSIRO involved in the global response to fight this deadly disease?

AAHL has highly specialised capabilities for working with zoonotic diseases. Scientists at AAHL first identified and characterised the deadly Hendra virus, which, like Ebola viruses, is classified as a ‘biosafety level four (BSL4) pathogen’- the most dangerous of viruses, without a known cure or vaccine. The team has since been integral in the development of the Equivac HeV vaccine, now being administered to protect horses and people in Australia.

Located in Geelong, AAHL is one of a handful of high-containment laboratories in the world capable of working on BSL4 pathogens. The facility was built to ensure the containment of the most infectious agents known. It is designed and equipped to enable the safe handling of disease agents such as Ebola virus, at the necessary high containment level.

For more information about the Ebola virus, see the World Health Organization fact sheet.


How are vaccines used in Australian agriculture?

Beef cattle

By Ian ColditzResearch Scientist, Livestock Health & Welfare

Approximately 140 vaccines are registered for use in livestock and companion animals in Australia. Many more animals are vaccinated each year than humans.

Vaccines are used in farm animals:

  • to protect livestock against endemic diseases
  • to modify reproductive performance (for instance by preventing sexual maturity in young males)
  • to improve food quality (for instance to reduce boar taint in pork)
  • to reduce the risk of transmission of diseases such as Hendra virus from animals to humans
  • to produce diagnostic reagents for use in pathology services
  • to produce therapeutic products for use in human and veterinary medicine.

Most decisions to vaccinate farm animals are made by livestock owners on a commercial basis. They balance the cost of vaccination against the risks of disease, reduced growth rates and compromised animal welfare.

An important benefit of vaccination – both for the farmer and more broadly for the community – is reduced reliance on antibiotics for treating infections in farm animals.

Adaptive immunity – learning from the environment

All animals are subjected to attack by microbes and parasites. In return, animals have well developed molecular and cellular defence mechanisms to fight off and kill infectious agents.

Within the time span of each animal’s life, it undergoes non-genetic (phenotypic) adaption to its local environment. Living in the environment leads to changes in physiology, behaviour and immune functions that enable the animal to fine tune its ability to cope and thrive.

Environmental conditions are learnt and remembered by the physiological, behavioural and immune systems of the animal. For the immune system, the lessons learnt from infection by a disease agent are remembered primarily by lymphocytes and are recalled when the animal is again exposed to the same disease-causing agent.

The recalled immune response is faster and more effective at clearing the infection. The lessons learnt from some infections such as orf virus (“scabby mouth”) in sheep are usually remembered for life, with a single infection inducing lifelong immunity to re-infection by the same disease agent. In contrast, some infections induce no effective immunity. In other instances immunity can wane over a matter of months.

Vaccines aim to induce protective immunity by controlled exposure to fragments of disease-causing organisms without exposure to the disease itself.

Passive immunity – animal vaccines helping humans

Suckling pigs

Image: Flickr / jennicatpink

Offspring receive a cultural inheritance of acquired knowledge about local disease threats from their mothers in the form of antibodies. Depending on the species, these are acquired via the placenta, egg yolk, colostrum or milk. Maternal antibodies provide passive immunity to offspring for the first few weeks of post-natal life. Some vaccines can be used during pregnancy in animals to enhance antibody transfer to offspring.

Antibodies from animals can also protect humans. Indeed, the first Nobel Prize in Physiology or Medicine was awarded to Emil von Behring in 1901 for his development of serum therapy. Von Behring used blood serum from sheep and horses immunised with Corynebacterium diphtheriae to treat patients suffering from diphtheria.

Following his example, the use of antisera raised in animals to treat humans for systemic diseases such as tetanus has been commonplace for many decades. In Australia, horses continue to be vaccinated to generate anti-toxins to tetanus, snake venoms and other toxins. Sheep are vaccinated to produce antivenin against rattle snake venom for use in America.

In the 1970s, it was found that oral ingestion of antibodies isolated from colostrum of cows immunised with human gut pathogens can protect humans from a range of gut infections. Products containing antibodies isolated from colostrum of immunised cows protect humans from rotavirus infections, traveler’s diarrhoea and dental caries. Similar products are also used in animals.

As the efficacy of antibiotics for control of bacterial infections has diminished, there has been a resurgence of interest in “passive immunisation”. This uses antisera produced in animals for prophylaxis and treatment of disease in humans and farm animals.

For instance, the prevalence and severity of diarrhoeal disease in humans can be reduced by daily ingestion of colostrum-based products from ruminants immunised with the disease-causing agent (and possibly also by consumption of fresh unpasteurized milk from the same animals. There is a very large potential to implement this technology in developing countries to help control diarrhoeal diseases.

Can vaccination and alternative farming mix?

Vaccination is usually used as part of an integrated disease control strategy in animals. Eradication and quarantine are the most effective strategies; however eradication is rarely achievable. Vaccination played an important role in eradication of equine influenza from Australia in 2008. Indeed Australia is the only country to have successfully eradicated this disease. Selecting breeding stock for resistance to disease is also a very important disease control strategy in farm animals.

As with all foods, medicines and therapies used in humans or animals, there are divergent views on the merits of using vaccines in animals. Some agricultural production philosophies, such as organic farming, discourage use of vaccines.

However, when mandated by regulatory authorities or in the face of an adverse disease history or when recommended by a veterinarian, the use of vaccines can be authorised by the organic certification entities Australian Organic and Organic Growers to aid in disease control on organic farms.

This approach provides neither an argument against organic farming nor against vaccination. A diversity of farming practices and production philosophies is likely to strengthen food security in the face of changing environmental threats and consumer preferences.

This article was originally published at The Conversation.

Read the original article.


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