The world has been keeping a very close eye on the Ebola virus for nearly a year now following the extraordinarily large outbreak seen in Western Africa, which has so far killed more than 8,000 people. One of the things that scientists and public health officials look at is how the genetics of the virus changes. This is because Ebola virus gene sequences have in the past allowed scientists to work out patterns of spread during an outbreak and when and where it likely originated.
While we would like to predict how the virus behaves directly from its gene sequences, we do not yet have the ability to do this. So when the BBC reported that “scientists tracking the Ebola outbreak in Guinea say the virus has mutated,” what did it really mean? Is the virus now more contagious and therefore better able to spread and even more of a worry for those fighting to stop it?
The answer is probably no. Of course the virus is mutating – mutation is a fundamental living process and all viruses do it. The news article contained no new surprising information but it did highlight a lack of understanding – or appreciation – of mutation in viruses and other organisms.
The truism
Mutation refers to the process of genetic change. Naturally, genetic information is encoded in a genome, which is made of either DNA or, in some organisms, a similar molecule called RNA. Genomes are important because they control almost every function of an organism: whether a human has blue or brown eyes; whether a fly has two or four wings, or whether a virus is sensitive to a drug or is resistant.
Genetic information is specified by strings of letters: A, T (U in RNA), C and G. If one sequence has ATCG and then changes to AGCG then we say it has mutated. This is one example of mutation and is referred to as a “single nucleotide change”. It is one of the most simple and common occurrences, especially in viruses such as Ebola.
Mutation is one of the most important processes in living things and is a central feature of things with genomes; without mutation there would be no life on this planet. This is because mutation supplies genetic diversity that can be acted on by evolutionary processes, such as natural selection, to change a particular function of an organism. This only happens when there is a selective advantage to the mutation and its change in function.
For example: a bacteria has a mutation that makes it resistant to an antibiotic that is used commonly – but under conditions without that antibiotic present, it will be no more adapted than its non-resistant cousin. But when you add the antibiotic into the mix then the resistant one will grow more than its sensitive cousin. Therefore it is said that mutation fuels evolution.
The importance of mutation
Some organisms mutate and can evolve at a much greater rate than other organisms. Viruses with genomes composed of RNA, like the Ebola virus, have especially high mutation rates. As it turns out, some other of these RNA viruses also pose a great threat to human health, including the influenza viruses, human immunodeficiency virus (HIV), Hepatitis C virus (HCV) and the measles virus.
One of the more pressing consequences of mutation is in a health setting. There are lots of known examples of mutations affecting human health, including the appearance of antiviral resistance in the influenza A virus, HIV, and HCV; the evasion of vaccine immunity of the influenza A virus between flu seasons, and the emergence of novel pathogens, namely in the origins of influenza pandemics, such as that of the H1N1 virus in 2009-10.
One of the other ways that mutation could do harm is by altering our capacity to diagnose an infection. Viral diagnostics is now commonly based on sequence-specific approaches, such as the polymerase chain reaction (PCR) and sequencing. If a mutation made a virus unable to be picked up by our lab diagnostics then it would be invisible to us.
Mutation and Ebola
During this outbreak, the Ebola virus has infected more than 20,000 people and led to the deaths of around 40% of those people. Recently the strategy to tackle Ebola has been three-fold: diagnose cases and isolate them; treat those confirmed cases, in isolation, using standard care and targeted antiviral drugs; and work to develop preventative strategies, such as a safe and effective vaccine. These strategies appear to have been effective at controlling the outbreak.
But no Ebola antiviral drug has so far completed phase III clinical trials, nor have any of the vaccines, although trials are due to begin in the affected countries.
If the Ebola virus were to mutate would this inhibit this current positive response? Or even one in the future? This is an important and valid point because it could impact our ability to control this epidemic and a similar one in the future, which is critical to save human lives.
Studies that have looked at genome mutations of the virus have shown changes in the genes that are also the targets for antiviral treatments, including those for vaccination. They build a strong case that we should be keeping an eye on these sequences now and into the future. But this is as far as our predictive capacity goes. Without testing how these mutations function in the virus under controlled experimental conditions we will not able to say for certain. However, studies of this sort have not yet been published.
Is Ebola becoming more contagious?
One big concern is whether or not the Ebola virus might evolve to become more contagious in the human population. Two ways this might be achieved is through the virus causing a less incapacitating disease that allows it to be shed more; or spreading via the airborne route rather than via bodily fluids.
Anavaj Sakuntabhai, a geneticist at the Institut Pasteur in France, which put out the warning about Ebola mutating, said they had now seen several cases where people didn’t have any symptoms at all – asymptomatic cases. “These people may be the people who can spread the virus better, but we still don’t know that yet,” he said. “A virus can change itself to less deadly, but more contagious and that’s something we are afraid of.”
But as yet, and this is something which Sakuntabhai admits, we have no evidence that the first is happening and that the virus is evolving to make people less sick. Increased detection of cases with less pronounced disease may be a function of our greater ability to diagnose Ebola in general. And it has been suggested that asymptomatic cases of Ebola virus infection may be more common than once thought.
It is still very unlikely that the Ebola virus is evolving to become airborne, despite the headlines. There is no precedent for a virus changing its mode of transmission and considering how many chances the Ebola virus has had to make such a change during this outbreak and previous ones, without doing so, suggests that evolution of this property might be one step too far.
Putting an end to the outbreak
Recently, the number of cases of Ebola has begun to drop across the three affected nations. This suggests that our interventions have begun to work. This positive response is thus most likely due to the excellent job that front line clinicians and lab staff have done in diagnosing, isolating and treating those patients with the standard care available. If this response continues then we may see the last case in this outbreak appear by the end of 2015.
So despite all of the worries around mutation, this outbreak is being controlled successfully and without targeted antiviral treatments in place. Our focus should be to finish the job in hand and put a stop to this epidemic using what we know works.
THE EXPLAINER
