Genes could influence Ebola survival, mouse study finds

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.