Genes may play a role in Ebola survival chances

Behind the Headlines

Friday October 31 2014

Ebola continues to be an issue of concern in West Africa

The current Ebola outbreak is largely confined to West Africa

"Genetic factors could play an important role in whether people survive the Ebola virus," BBC News reports. Researchers found around one in five mice remained unaffected by the infection.

Researchers investigated how mice with a different genetic make-up responded to Ebola infection. The research involved eight research strains of mice said to represent the majority of genetic variation seen across major mouse species. They were infected with Ebola and had their disease response examined.

The researchers found mice with different genetic profiles show variable disease response, ranging from complete resistance to infection with full recovery, to the disease being fatal.

Mice with resistance and those who died from the disease tended to have differences in the activity of certain genes, which was associated with differences in their immune and inflammatory response.

But the findings do not necessarily mean a similar pattern will be seen in humans, who have quite different genetics to mice.

Environmental factors such as access to good healthcare and hygiene standards (which, sadly, are of a low standard in West Africa), as well as the age, health and fitness of the person, are also likely to play a significant role in how infection with Ebola affects any individual.

Nevertheless, learning more about the genetic and immune responses to the Ebola virus could help contribute to the future creation of an effective anti-viral treatment.

Experts believe Ebola is highly unlikely to spread within the UK. To understand why, read Why Ebola risk is low for people in the UK.

 

Where did the story come from?

The study was carried out by researchers from the University of Washington and other research institutions in the US.

It was funded by grants from the US National Institute of Allergy and Infectious Diseases, the National Institutes of Health, and the Intramural Research Program of the National Institute of Allergy and Infectious Diseases, National Institutes of Health. 

The study was published in the peer-reviewed scientific journal Science Express on an open access basis, so it is free to read online.

The UK media's stories generally provide an accurate summary of the research, with most stating early on that the study was in mice.

However, the Mail Online's headline, "Will Ebola kill you? It depends on your genes," is overly conclusive and does not take account of the uncertainty of the research or its unproven applicability to people.

 

What kind of research was this?

This was an animal study investigating how mice with a different genetic make-up responded to Ebola infection in different ways.

The researchers explain how most animal studies examining the disease development of Ebola, or looking at the effectiveness of vaccines or treatments, have had to use primates or small mammals.

This is because when mice have been infected with Ebola in the laboratory, they don't demonstrate the same haemorrhagic syndrome (for example, complete dysfunction of the clotting system in the body) that occurs in humans.

This study specifically examined the role of host genetics in determining the severity of disease caused by Ebola infection.

 

What did the research involve?

This study involved infecting genetically diverse mice with different strains of Ebola to see if their genetics influenced the symptoms they developed, and whether they ultimately lived or died.

The study used mice from what is called the Collaborative Cross (CC) resource, a genetically diverse group of inbred mice obtained from the cross of eight mouse strains – five said to be classic laboratory strains, and three wild-type (found in nature) strains.

The eight "founder" mice strains are said to represent 90% of the common genetic variation seen across three major mouse species.

The researchers infected the eight CC founder strains with two strains of Ebola virus – a mouse strain and the wild-type strain, which doesn't normally cause haemorrhagic syndrome in mice.

They carried out a detailed analysis of the disease symptoms and the disease response in the mice.

 

What were the basic results?

When infected with the mouse strain of Ebola virus, the researchers observed different disease responses across the mice, ranging from complete resistance to infection to fatal disease. Some of the fatal cases developed disease changes consistent with haemorrhagic syndrome, while others did not.

The researchers performed more detailed analysis on two of the mouse lines – those resistant to disease and those that developed Ebola haemorrhagic fever.

Mice from both of these lines lost about 15% of their body weight in the five days following infection. The susceptible mice died on day five or six, while resistant mice fully recovered two weeks after infection.

Those that died demonstrated disease features consistent with Ebola haemorrhagic fever, including internal bleeding, prolonged blood coagulation times, spleen enlargement and liver discolouration. The resistant mice had no disease changes or alteration in their liver.

On further study, the researchers found differences in the inflammatory and immune response of mice susceptible or resistant to infection. This difference in response seemed to be mediated by differences in gene expression.

In particular, expression of the Tek gene in the liver was lower in the susceptible mice, and this was associated with onset of haemorrhagic disease. 

When infected with the wild-type Ebola strain, however, neither the susceptible nor resistant mice developed clinical disease. The animals had very low levels of the virus in their liver and spleen – up to 1,000 times lower than their levels when infected with the mouse strain.

At five days after infection, there was no longer any virus detectable, indicating that the wild-type Ebola virus is not able to replicate in mice.

 

How did the researchers interpret the results?

The researchers concluded that their results indicate genetic background determines susceptibility to Ebola hemorrhagic fever.

 

Conclusion

This research across mouse strains demonstrates that mice with different genetic profiles show variable disease response after infection with the Ebola virus. Responses ranged from complete resistance to infection with full recovery, to fatal disease, with or without changes consistent with Ebola haemorrhagic fever.

When comparing the mice that were resistant with those that developed fatal Ebola haemorrhagic syndrome, they found differences in the activity of certain genes, which was associated with different immune and inflammatory response.

However, these results in mice should not be extrapolated too far at this stage. The findings that different genetic strains of mice respond to Ebola infection in different ways does not mean the case will be exactly the same in people, who have quite different genetics to mice.

Genes may play a more or less important role in Ebola symptoms and survival in people, but at this stage we simply don't know.

Similarly, the different infection responses were seen only when mice were infected with the mouse strain of Ebola. The wild Ebola strain was not able to replicate in mice, further demonstrating the dissimilarities to human disease.

As BBC News reports, Andrew Easton, Professor of Virology at the University of Warwick, said the study "provided valuable information, but the data could not be directly applied to humans because they have a much larger variety of genetic combinations than mice".

Even if in humans (as in mice) our genetics play a role in how we respond to Ebola infection, it is unlikely to provide the whole answer. Factors such as the environment we live in – such as healthcare and hygiene standards – and our own underlying age, health and fitness are likely to play a large role in how we respond to Ebola infection.

Nevertheless, this study contributes to the wider understanding of Ebola, and may help direct further research examining the causes and effects of this devastating disease, as well as effective treatments at some point in the future.

Analysis by Bazian. Edited by NHS Choices. Follow Behind the Headlines on Twitter. Join the Healthy Evidence forum.

Analysis by Bazian

Edited by NHS Choices

Links to the headlines

Ebola virus: Genes 'play significant role in survival'. BBC News, October 31 2014

Ebola outbreak: Ebola may not be a deadly disease for everyone, scientists find. The Daily Telegraph, October 31 2014

Will Ebola kill you? It depends on your genes: Scientists discover DNA could determine if victims live or die. Mail Online, October 31 2014

Links to the science

Rasmussen AL, Okumura A, Ferris MT, et al. Host genetic diversity enables Ebola hemorrhagic fever pathogenesis and resistance. Science. Published online October 30 2014

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