Wednesday, October 22, 2014

Scientists found the origins of the Ebola outbreak — by tracking its mutations

Sierra Leone government burial team members wearing protective clothing carry the coffin of Dr Modupeh Cole, Sierra Leone's second senior physician to die of Ebola. Carl De Souza/AFP/Getty Images

One of the big mysteries in the Ebola outbreak in West Africa is where the virus came from in the first place — and whether it's changed in any significant ways. These unanswered questions could be making it more difficult to diagnose the disease and find treatments.

Now scientists are starting to get some answers. In a new paper in Science, researchers reveal that they have sequenced the genomes of Ebola from 78 patients in Sierra Leone who contracted the disease in May and June. Those sequences revealed some 300 mutations specific to this outbreak.

The new analysis could help determine if the virus' behavior has changed — and provide information for future diagnostic tests and treatments.

Among their findings, the researchers discovered that the current viral strains come from a related strain that left Central Africa within the past ten years. And the research confirms that the virus likely spread into Sierra Leone when women became infected after attending the funeral of a traditional healer who had been treating Guinean Ebola patients.

The current Ebola outbreak in West Africa is the worst on record. It has hit four countries, including Sierra Leone, infected approximately 3,000, and killed about 1,500 people. And so far, there is no sign of it slowing down.

The fact that the researchers published the sequence of the Ebola genomes in mere months contrasts with the typically slow pace of scientific research. "We’re trying to do this as fast as possible," says co-senior author Pardis Sabeti, a biologist at MIT and Harvard. This new data increases the number of public Ebola virus sequences fourfold.

The main impact of the paper will be as the foundation of research for years to come as other projects try to sort out what all of these genetic sequences — and their hundreds of mutations — really mean.

The paper is also a sad reminder of the toll that the virus has taken on those working on the front lines. Five of the authors died of Ebola before it was published. All were affiliated with Kenema Government Hospital in Sierra Leone.

What genetic sequences can tell us about Ebola

Ebola tree lineage

(Gire, SK, et al. Science, August 28, 2014.)

Viruses randomly mutate over time. This is completely normal for viruses, and there's no reason to think that Ebola's mutation rate is anything weird or unusual.

Scientists can use these mutations as markers to piece together how the Ebola virus has traveled from person to person. Because they know the general mutation rate of the virus, they can also pin down the dates of when the disease spread.

So what has this analysis revealed? Using genetic sequences from current and previous outbreaks, the researchers mapped out a family tree that puts a common ancestor of the recent West African outbreak some place in Central Africa roughly around 2004. This contradicts an earlier hypothesis that the virus had been hanging around West Africa for much longer than that.

The data, on the whole, supports what epidemiologists have already deduced about how the virus spread into Sierra Leone. More than a dozen women became infected after attending the funeral of a traditional healer who had been treating Guinean Ebola patients and contracted the disease.

One surprise from the paper is that two different strains of Ebola came out of that funeral. This suggests that either the healer was infected with two different strains or that another person at the funeral was already infected.

As Ebola then traveled across Sierra Leone, a third strain of the virus appeared.

Why having Ebola gene sequences is helpful

Some Ebola diagnostic tests have been designed to detect areas that have mutated in the Ebola virus samples from this outbreak, raising the possibility these tests might be losing accuracy. One of the things Sabeti plans to do next is test whether that's actually the case.

Diagnosing Ebola can actually be more difficult than it might sound. The disease often looks like a lot of other feverish illnesses that can be common. And at a later stage, only some patients end up bleeding.

However, it's essential to know who has it as soon as possible, especially so that health-care workers can use appropriate procedures to prevent transmission to themselves and others. So accurate diagnostic tests are absolutely needed.

Researchers are also planning to study the mutations to see if any of them are affecting Ebola's recent behavior. The number of mutations found is completely normal, and it isn't necessarily the case that they'll have a big effect. But it's possible that something intriguing could turn up.

For example, this outbreak has had a higher transmission rate and lower death rate than others, and researchers are curious if any of these mutations are related to that. (Right now, social factors are thought to be the main causes of these two changes.)

"It sets the stage for the next few years of research that will reveal the differences between this virus and previous versions of Ebola virus," says Erica Ollmann Saphire, who researches Ebola and similar viruses at The Scripps Research Institute in La Jolla, California.

"My laboratory will be using this sequence information to understand the molecular effects of these mutations," she says. "We will also be looking at our pool of antibody therapeutics beyond ZMapp to ensure that candidate cocktails are optimally effective against these circulating strains."

Those working on other long-term projects involving vaccines should also find this information helpful.

The longer Ebola circulates, the more opportunities it has to change — possibly for the worse

Although Ebola's mutation rate itself isn't anything unusual, the longer it's circulating in people, the more chances it will have to randomly come up with a mutation that it will find beneficial — possibly to the detriment of human health.

"You never want to give a virus that kind of opportunity," Sabeti says. "We hope that this work opens up new doors for more people to work together to stop this virus now."

Update: Clarified that the speed of publication, not necessarily the speed of sequencing, is remarkable.

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