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Genes could influence Ebola survival, mouse study finds

3 November 2014
Appeared in BioNews 778

Genetic factors could explain why some people survive the Ebola virus, a study in the USA suggests.

The researchers infected genetically diverse mice with a species-specific strain of the virus. Some developed severe illness and died, some survived, but a few seemed to resist the disease very strongly.

Two genes involved in blood coagulation were expressed differently in the susceptible and resistant mice, a finding that may have implications for humans.

Study leader Professor Michael Katze at the University of Washington, told Reuters: 'These mice were infected with exactly the same dose by exactly the same route by the same investigator. The only thing that was different was the genetic background.'

Forty-seven distinct mouse lines were used in the research and were infected with a mouse form of the same Ebola virus species that is currently epidemic in West Africa. All of the mice lost weight in the first few days after infection. However, 19 percent regained this weight within two weeks and showed no pathological evidence of the disease. On the other hand, 70 percent were severely affected and developed liver inflammation, prolonged blood clotting and haemorrhagic fever. Over half of all mice in that category died.

Dr Angela Rasmussen, another study leader, said: 'The frequency of different manifestations of the disease across the lines of these mice screened so far are similar in variety and proportion to the spectrum of clinical disease observed in the 2014 West African outbreak.'

She also told Reuters that in classical lab mice 'Ebola kills the animals but it doesn't produce haemorrhagic disease'.

In their study, the researchers selected two mouse lines for further analysis, one of which was susceptible to lethal haemorrhagic fever, and the other was resistant. While the resistant mice only suffered from initial weight loss and recovered after 14 days, the susceptible mice died after five to six days, and had severely damaged livers, blood clotting defects, internal haemorraging and enlarged spleens.

Although both groups of mice had similar levels of viral RNA in their liver and spleens, ten times more infectious viral particles were found in the organs of susceptible mice. Accordingly, the researchers think that the resistant mice were able to inhibit virus replication late on in the replication process.

The study also reported differences in the inflammatory and immune responses between mouse lines which seemed to be mediated by differences in gene expression.

Dr Rasmussen told The Scientist that her team hoped 'to find expressions of gene signatures that can be associated very definitively with one outcome or another. Way down the road, these types of signatures could potentially be diagnostic or prognostic tools'.

Professor Jonathan Ball, professor of molecular virology at the University of Nottingham, who was not involved in the study, said that, in particular, 'the finding that levels of expression of a gene involved in coagulation differs between mice showing different severity of disease symptoms is really intriguing'.

'It will be important to see if a similar phenomenon is happening in humans,' he added.

The study was published in the journal Science.

SOURCES & REFERENCES
Ebola virus: Genes 'play significant role in survival'
BBC News |  31 October 2014
Expert reaction to genetic influence on Ebola outcome in mice
Science Media Centre (press release) |  30 October 2014
Genetic factors behind surviving or dying from Ebola shown in mouse study
Eurekalert (press release) |  30 October 2014
Host genetic diversity enables Ebola hemorrhagic fever pathogenesis and resistance
Science |  30 October 2014
Individual genetic differences may affect Ebola survival - study
Reuters |  31 October 2014
Modeling Ebola in Mice
The Scientist |  30 October 2014
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