Bat’s immunity may hold key to preventing future Ebola outbreaks

By Michelle Baker, CSIRO

Bats can harbour viruses such as Ebola and don’t display clinical signs of disease. Image - Janelle Lugge

Bats can harbour viruses such as Ebola and don’t display clinical signs of disease. Image – Janelle Lugge

Bats are the natural host species for Ebola and a variety of viruses, many of which can be fatal when transmitted to humans. More than 100 viruses have been identified in bats and this number is rising each year.

African fruit bats first transmitted Ebola virus to primates and other species through contact with bat droppings, half-eaten fruit or bodily fluids of diseased bats. People are thought to have contracted the virus through contact with infected bats and primates. Subsequent person–to-person transmission occurs through direct contact with infected body fluids: blood, saliva, mucus, vomit, urine or faeces.

Interestingly, bats have the ability to harbour viruses such as Ebola and don’t display clinical signs of disease. Yet once the virus infects other species, it has the potential to cause widespread death and disease. How is it that bats are resistant to a disease that kills up to 90% of people it infects?

Ebola virus infection

The impact of Ebola virus in people is largely the result of the activation of the immune system, rather than the virus itself. During the initial stages of infection, Ebola shuts off the immune response to the virus, resulting in rapid viral replication and a delay in the production of antibodies.

The immune system is initiated only once the virus is out of control and then results in over-activation of the immune response. Although the role of the immune system is to eliminate the virus, when it is activated at extreme levels it becomes damaging to the host – in this case, an infected patient.

Like all haemorrhagic fevers, this results in widespread tissue damage, leading to internal and external bleeding, decreased kidney and liver function and ultimately, in many cases, death.

Therapies

The Ebola outbreak in West Africa is the largest ever recorded and is continuing to accelerate. Researchers and drug companies are racing to develop treatments and vaccines targeting the Zaire ebolavirus, the strain that is causing the current outbreak.

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The Ebola vaccine trial results will be assessed next month. Image Point Fr/Shutterstock

The first human trial to establish the safety of the vaccine and assess the immune responses of volunteers is underway. The researchers hope that by November there will be enough data to make an informed decision about whether to deploy the vaccine in Western Africa.

So far, studies in monkeys have demonstrated that the vaccine provides protective immunity for up to ten months.

Unlocking the bat immune system

Studying how bats control viral replication may unlock alternative mechanisms for tackling Ebola as well as other new and emerging infectious diseases. Increasing antimicrobial resistance of viruses, bacteria and fungi, for instance, is becoming a global concern and we need to think creatively to find solutions.

Bats and viruses have achieved an equilibrium that allows them to co-exist. Clues from studies of bat genomes have revealed differences in genes associated with the very early immune response that could help bats respond to infections. These genes appear to be evolving at a faster rate in bats compared with other species, providing evidence that they are likely co-evolving with the viruses that bats carry.

Functional differences in the immune system may also play a role. Unlike humans and mice, which activate their immune systems only in response to an infection, bats appear to have certain components of their immune system constantly switched on. This may allow bats to control viral replication much more efficiently compared with other species.

If we can redirect the immune responses of other species to behave in a similar manner to that of bats, the high death rate associated with diseases such as Ebola could be a thing of the past.

It’s tempting to look to culling as the answer to deal with bats as the natural hosts of Ebola. This suggestion was made during the spillover of Hendra virus from bats to horses in Australia. But it is not the answer; bats are an extremely successful group of mammals, making up 20% of all mammalian diversity. They are critical to ecosystems, with roles in insect control and pollination.

Rather than persecuting bats, we need to unravel the secrets of the success of this group of mammals. Understanding how bats control viral replication would not only assist in developing future therapeutics but may also help predict transmission events from bats into human and animal populations.

Michelle Baker receives funding from The Australian Research Council

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


We still don’t know if domestic animals can spread Ebola

 

Man holding dog

It’s unclear whether Spanish dog Excalibur, pictured here with owner Javier Limon (husband of Ebola-infected nurse Teresa Ramos), was infected. EFE/PACMA

By Michelle Baker, CSIRO

Spanish authorities have euthanised the dog of Madrid nurse Teresa Romero Ramos, who contracted Ebola. The 12-year-old dog, Excalibur, was not showing symptoms and was not tested for Ebola. But he lived with Romero Ramos when she became ill and was destroyed as a precaution, despite widespread protests.

This has raised questions about the role domestic animals might play in the spread of Ebola. But before we get to dogs and cats, we need to start with bats – the natural host of Ebola and a number of other viruses including Hendra virus, rabies, SARS (sudden acute respiratory syndrome) and MERS (Middle East respiratory syndrom).

African fruit bats were established as the host of Zaire Ebola virus after antibodies were detected in a number of species. Though interestingly, bats are not affected by the virus.

Intermediate hosts in viral transmission

For many of the viruses carried by bats, there is no evidence of direct bat-to-human transmission. More often than not, an intermediate host – or spillover host – gets infected following contact with infected bat material.

Spillover hosts generally develop severe disease and are capable of shedding the virus in large quantities, which can pass to people who come in close contact with secretions from the infected animals.

Image by jomilo75/Flickr, CC BY-NC-ND

Ebola originated in African fruit bats.
jomilo75/Flickr, CC BY-NC-ND

Intermediate hosts can include horses in the case of Hendra virus, pigs for Nipah virus and palm civets in the case of SARS.

For Ebola, it is believed that contact with wild animals including gorillas, chimpanzees and antelope have been the source of human infection.

Although the intermediate host is known for many bat-borne viruses, the role that other domestic animals play in the transmission cycle is largely unknown.

Are domestic animals a risk?

During previous Ebola outbreaks, scientists have found virus specific antibodies in dogs. But the canines showed no symptoms. It’s still unclear whether dog-to-human transmission is possible, as is the mechanism by which dogs and other domestic animals become infected.

A similar situation occurred in Australia in 2011 when Hendra virus specific antibodies were detected in a dog from a property where Hendra virus-infected horses were located. Again, we know little about the infection dynamics of this virus in dogs.

While cats are not resistant to Hendra virus disease, natural transmission from infected bats or horses to cats has not been demonstrated.

A complicating factor is that people who recover from infection with Hendra virus can experience a subsequent relapse in disease. Whether viruses such as Ebola or Hendra virus can also lie dormant in domestic animals and reactivate at a later time point remains to be investigated.

Opportunities for transmission

While research is underway, the mechanisms involved in the transmission of Ebola and other bat-borne viruses to intermediate hosts is currently poorly understood. It seems to occur as a result of contact with bat secretions or partially eaten fruit which the bats chew and drop to the ground.

But the transmission of viruses from bats to other species depends, to a large extent, on opportunity.

Palm civets can be intermediate hosts of SARS.  Kabacchi/Flickr, CC BY

Palm civets can be intermediate hosts of SARS.
Kabacchi/Flickr, CC BY

Bats and viruses have long coexisted but interactions between bats and other species including humans have occurred only relatively recently. Urbanisation and deforestation has resulted in increased encroachment of humans and domestic animals into bat habitats.

Similarly, live animal markets such as those in Southern China, where SARS was detected in palm civets, are associated with close contact between a variety of different species and provide an ideal melting pot for spillover to take place.

Social and cultural practices also play a role in viral transmission including the consumption of “bush meat” from wild animals including non-human primates and bats.

In each of these situations, humans have provided the opportunity for interspecies contacts which would not have otherwise occurred.

Bats have an important place in our ecosystem, and there is so much we can learn from them. To help manage and prevent future outbreaks, we need a more comprehensive, science-based understanding of risks associated with the increased interaction of people and animals with wildlife.

The Conversation

Michelle Baker receives funding from The Australian Research Council.

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


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.


From animals to humans: understanding Ebola virus

An artificially coloured electron microscope image of Ebola virus .

Ebola – an artificially coloured electron microscope image of the virus.

By Gary Crameri and John Lowenthal

There is growing global concern as the West African country of Guinea battles to contain a deadly outbreak of Ebola virus, yet another disease of animal origin, which is threatening the lives of their people.

Previous outbreaks of the virus have been localised in Africa, but there are growing concerns that it could spread further with cases now being diagnosed in the neighbouring countries of Sierra Leone and Liberia. So what exactly is known about this disease?

Ebola virus 101

Ebola virus, also known as Ebola hemorrhagic fever, is a highly infectious and contagious illness with a fatality rate in humans of up to 90 per cent.

One of the most lethal infectious diseases known, it was first discovered in 1976 in two simultaneous outbreaks – one in Nzara, Sudan and the other near the Ebola River in Zaire – now the Democratic Republic of Congo. Since then over 1600 deaths have been recorded.

The Ebola virus is feared for its rapid and aggressive nature. When the virus gains access to the human body, it starts attacking the vascular system and the walls of the blood vessels. This prevents blood from clotting causing internal or external bleeding.

Diagnosing Ebola in its early stage is difficult. Its early flu-like symptoms such as headache and fever are not specific to Ebola virus infection and are seen often in patients with more commonly occurring diseases in the region like malaria and cholera.

Where does it come from?

Ebola virus is a zoonotic disease, meaning it passes from animals to people. As with the respiratory diseases SARS and MERS and the Hendra virus, bats have been identified as the reservoir host. Four of the five subtypes of Ebola virus occur in an animal host which is native to Africa.

There is good evidence that other mammals like gorillas, chimpanzees and antelopes are probably the transmission host to humans but the mechanism of their infection from the fruit bats is not certain.

Ebola can then spread to humans through close contact with the blood, secretions, organs or other bodily fluids of infected animals or through people consuming an infected animal.

Once a person is infected, the virus can only be spread to other people by very close contact, including direct exposure with bodily fluids or through exposure to objects that have been contaminated with blood or infected secretions. Infected individuals can be infectious for weeks after recovery from the acute illness.

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.

Scientists working on zoonotic agents wearing biosafety suits

Scientists working on zoonotic agents require the highest level of biosafety

The next big virus?

A number of emerging infectious diseases are causing issues on a global scale. We’ve also seen outbreaks over the past few months of Hendra virus, MERS and two avian influenza viruses, H7N9 and H5N1.

Recent growth and geographic expansion of human populations and the intensification of agriculture has resulted in a greater risk of infectious diseases being transmitted to people from wildlife and domesticated animals. Moreover, increased global travel means there is a greater likelihood that infectious agents, particularly airborne pathogens, can rapidly spread among the human population. Together, these factors have increased the risk of pandemics – it’s not so much a matter of if, but when.

The World Health Organization has warned that the source of the next human pandemic is likely to be zoonotic and that wildlife is a prime culprit.

While the current list of known emerging infectious diseases is a major concern, it’s the unknown viruses, with a potential for efficient human-to-human transmission that pose the biggest threat.

Fortunately Australia has a robust system to deal with an emergency disease outbreak, including our very own Australian Animal Health Laboratory, a globally recognised biosecure zoonosis laboratory, and scientific and medical experts linked via a national veterinary and public health laboratory network.


Bat virus could hold key to Hendra

Australian scientists have discovered a new virus in bats that could help shed light on how Hendra and Nipah viruses cause disease and death in animals and humans.

The new virus – named ‘Cedar’ after the Queensland location where it was discovered – is a close relative of the deadly Hendra and Nipah viruses.

However, CSIRO’s initial studies have discovered one surprising key difference – the Cedar virus does not cause illness in several animal species normally susceptible to Hendra and Nipah.

Cells infected with Hendra virus (left) and with Cedar virus (right). Hendra virus is the more effective at fusing cells (circled) and spreading its infection. More individual cells remain intact (circled) with Cedar virus and it doesn’t spread nearly as extensively.

This tantalising difference may help scientists understand how to better manage and control its deadly cousins. The findings have been announced today in the journal, PLoS Pathogens, publishedby the Public Library of Science.

Mr Gary Crameri, research scientist with the bat virus team at CSIRO’s Australian Animal Health Laboratory in Geelong, Victoria, said the new discovery had significant potential implications for protecting animals and humans from the Hendra and Nipah viruses.

“The significance of discovering a new henipavirus that doesn’t cause disease is that it may help us narrow down what it is about the genetic makeup of viruses like Hendra and Nipah that does cause disease and death,” Mr Crameri said.

“The more that we can learn about bat-borne viruses, the better chance we have of developing anti-virals and vaccines to help protect human health, Australia’s livestock industry and our export trade from the threat of current and emerging animal diseases.

“Over 70 per cent of people and animals infected with Hendra and Nipah viruses die. This ranks henipaviruses amongst the deadliest viruses in existence, yet little is known about just how such viruses actually cause disease or death.”

It is still too early to rule out the possibility that Cedar virus may cause illness and death in horses or other animals.

The discovery was a result of a close partnership with Biosecurity Queensland which played an important role by collecting and screening samples from bat colonies across Queensland.

“Field work with bats is an essential part of research into identifying new viruses,” Dr Hume Field of Biosecurity Queensland said. “Bats are being implicated as the natural host of a growing number of viruses in Australia and overseas, yet they appear to tolerate infection themselves making bat research increasingly important.”

Bats have been identified as playing a role in the spread of viruses including Ebola, Marburg, SARS and Melaka yet they are an essential part of our diverse ecosystem through their role as pollinators, seed dispersers and insect regulators.

The discovery is part of ongoing research by CSIRO to target diseases that threaten our animals, people and the environment and is part of CSIRO’s wider biosecurity effort. It follows CSIRO’s development towards a horse vaccine against Hendra virus.

MEDIA:

Pamela Tyers, CSIRO Australian Animal Health Laboratory

Mb: 0488 995 023 E: Pamela.Tyers@csiro.au


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