Cellou Binani/AFP/Getty Images
By Debora MacKenzie
Ebola was already bad enough. Now virologists have found that it quickly learns to spread more readily among humans – and in the process, becomes a deadlier disease. The West African epidemic that started in 2014 was ended by simple isolation measures. Much more of such viral evolution, and those may not have been enough.
That Ebola epidemic was by far the biggest ever, striking at least 28,600 people and killing 11,310. From the start, virologists feared that a large number of cases would give the virus unprecedented opportunities to adapt to humans.
For a virus, adapting means getting better at spreading. Ebola, like bird flu and other disease germs from animals, is usually deadly in people, but not adept at transmitting. At the start of the West African epidemic, New Scientist warned that “the more human cases, the more chances it will get… to evolve to become more transmissible in humans“.
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That seems to be exactly what happened. The epidemic started in Guinea, and then invaded Sierra Leone when there were only around 100 cases. At that point, the virus acquired a mutation called A82V in the part of its main surface protein that binds to the cells it invades.
It was the first major epidemic in which the pathogen’s genes were sequenced virtually in real time throughout – and this revealed that A82V was maintained in subsequent cases. The appearance of the mutation coincided with acceleration of the epidemic, as did its later introduction back into Guinea.
Using computer models of viral evolution, geneticists concluded that this could have been merely down to chance. But that, says Jeremy Luban at the University of Massachusetts in Worcester, was before anyone “got their hands dirty and found out what it does.”
Four times as infective
This week, both Luban’s team and a separate one led by Jonathan Ball at the University of Nottingham, UK, report that A82V allows the Ebola virus to infect human and other primate cells up to four times more efficiently than the unchanged virus.
They also found that several subsequent mutations did little on their own, but increased infectivity still further when they accompanied A82V – suggesting that the virus was under evolutionary pressure to infect humans more readily. More infection means more replication, which can also lead to more transmission.
The association between the mutations and the epidemic’s subsequent rampage might, however, have still been mere chance. The teams cannot formally prove that the mutations increased the virus’s evolutionary fitness without tests in experimental animals – which they want to do, in high-containment labs.
But Luban argues that all the evidence points to the mutation contributing to the severity of the epidemic. “The small bit of protein that touches the human receptor changes in a species-specific way, only after unprecedented human-to-human transmission, increases human cell infectivity fourfold, and happens to be the only form of the virus that invaded six more countries,” he says.
Ball shares this view. “Given that A82V plays a key part in receptor binding, and that we also found other mutations that improved on it, I find it difficult to conceive that this was not adaptation that was selected for,” he says. “It made the virus more fit.”
Nastier strain
The mutation may also have made the virus nastier. Luban’s team analysed 200 cases in which viral genes and the course of the disease were known. People with A82V had more of the virus in their blood, and were nearly three times more likely to die.
This isn’t surprising, because Ebola is mainly transmitted in body fluids from severely ill people or corpses, says Andrew Read at Pennsylvania State University in University Park. “If the vast bulk of transmission is via disease severity and death, adaptation will promote more virulent Ebola,” because that will produce more severe disease and death, and therefore transmit more virus.
The good news is that the A82V mutation disappeared when the epidemic ended – except where it lingers in the eyes or testes of survivors, which could be happening through its talent for invading human cells. But A82V arose early in the epidemic, which means either this mutation or one with similar effects will arise in the next one, says Ball.
That, says Read, is why we need to snuff out any future outbreak quickly. Vaccines have been developed, but the teams also report that West African Ebola mutated in ways that might blunt the effectiveness of vaccines, or our own immune responses. It seems that our battle with the Ebola virus has only begun.
Journal references: Cell, DOI: 10.1016/j.cell.2016.10.014; Cell, DOI: 10.1016/j.cell.2016.10.013
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