Outbreak Origins

How did Ebola and HIV first infect humans? Analysing viral DNA holds the answers to their evolutionary history.
26 August 2014

Interview with 

Alexei Drummond, Department of Computer Science University of Auckland

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The ebola filovirus, which causes ebola haemorrhagic fever, a frequently fatal infection carried by fruit bats.

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Analysing the DNA of viruses like Ebola or HIV can tell us a lot about how theyEbola virus are evolving, and also about how they first started affecting humans. Alexei Drummond, Professor of Computational Biology at the University of Aukland explained how understanding DNA can tell us a lot about outbreaks...

Alexei -   Specifically, we do research ourselves on viruses, HIV, hepatitis C, influenza.  And those viruses are particularly interesting because they're examples of what we call measurably evolving populations.  I mean, influenza 2 years ago to today, there's been about 1% evolution.  So, the genomes are 1% different now than they were just 2 years ago.  Now, that's about the same difference as between humans and chimpanzees and it's happened in 2 years.  So, we're talking about a million times faster than things like us are evolving.  And so, that creates a huge problem and one of the reasons we don't have any vaccine for influenza yet, we get a flu jab which each year, which is designed for that season, it actually doesn't work very well because it's already moved on a bit from when we designed that flu jab.  And so, this is a major issue obviously and one that our software tries to track and help.

Chris -   What sorts of things are you able to wind the genetic clock back on to sort of work out when they come from?  If I asked you for example where you think HIV - the virus that causes AIDS, came from and how long ago, could you apply your sort of technology to the virus to work out how fast it's evolving and then wind its genetic clock back?

Alexei -   Absolutely.  I mean, that's one of the first of major applications of the software that we've developed.  It's now fairly well established that the HIV strains that are circulating in humans today had about 4 or 5 origins, all from Africa around 100 years ago.  And it didn't come into - for instance the Americas until about '60s or '70s based on genetic evidence.  But that was still 10 or 15 years before we recognise that there was such a thing as HIV and that was the cause of AIDS.  Part of the reason for that is because you don't die from the HIV virus.  You die from pneumonia or something else, because it destroys your immune system and it takes 10 or 15 years for that to happen.  So, a lot of people would've had HIV in the '60s and the '70s in the US and were undiagnosed and probably died undiagnosed.

Chris -   But 100 years ago is not very long for a virus of the sort of impact that HIV has had to have occurred.  So, where it come from then 100 years ago to pop up out of existence?

Alexei -   So, HIV is related to the simian amminodeficiency viruses.  SIVs which are found in many different species of monkeys and apes in Africa.  And so, there's like I said, at least 4 major introductions into humans and probably, hundreds actually that got into one human, but never continued to spread within humans.  And so, this is constantly happening.  We're having cross species transmissions.  What the genetics tells us is, what time that the ones that have been successfully able to spread have come from.

Simon -   We're talking romantic interludes here?  I'm sorry to ask the dumb question, but...

Alexei -   Well, one of the major things happening in Africa right now is there's an increase in bushmeat trade and bushmeat trade is people going in to find food from wild sources within the jungle and what you get is contact between blood essentially most of the time - blood contact, eating wild game that is infected is one of the ways that you can get HIV.  It's also the way that probably Ebola sometimes has been getting into...

Chris -   I was going to ask about this.  This is a very modern kind of current threat with Ebola, the worst outbreak we've ever seen this year, currently occurring in Africa, of Ebola.  So, what does your research reveal about where that may have come from and how old that is?

Alexei -   So, the Ebola that's currently spreading in Guinea and a few other countries is genetically related to Ebola Zaire which was first - the first identified human outbreak was in 1976.  So, we've known about this genetic strain for almost 40 years now and the outbreaks have been occurring small outbreaks of a few hundred cases every 5 or 10 years since then.  To put that in perspective, Ebola is a fairly typical RNA virus.  It evolves maybe 10 times slower than HIV or influenza.  Its evolution rate is say, 1% change in 10 or 15 years.  It's got the same as measles.  The other thing to put in perspective is although maybe a couple of thousand people in that 40 years have died from Ebola.  Influenza kills half a million a year.  AIDS related illness takes 1.4 million people per year.

Simon -   Is there an idea that Ebola though could speed up?  So, could Ebola become incredibly virulent?

Alexei -   Typically actually, when a virus comes into a new species, the pattern is for virulence to decrease, not increase.  But in terms of the evolutionary rate, this is really determined by fundamental features of how the virus translates and how it's spread and the way it copies its genome.  These things done change over time.  So, we know a lot about filoviridae - the group of viruses that Ebola comes from.  That pattern of 1% for 10 or 15 years.  We now have data from '76, from the '80s, the '90s, 2002, 2006 and the latest outbreak.  It's very clear what the pattern of the evolution of that virus is.  I think probably, the only reason we don't have a vaccine for it because in the scale of things, it hasn't been a major disease compared to many of these other ones.

Chris -   Where did it come from in the first place?

Alexei -   It's not naturally a human virus.  It's a virus that has some sort of wild animal reservoir.  You can find Ebola in monkeys and chimpanzees, gorillas, but they also get disease.  So, it's probably not their natural reservoir either.  They get very bad disease.  It's most likely they come from fruit bats.  A number of different species of fruit bats have been found to have Ebola virus within them at high prevalence and they're asymptomatic.  So, it very much looks like the virus has adapted to them.  It's not very good for a virus to kill off its host.  It makes it hard for it to spread well.  The Ebola doesn't spread well in humans because it's got such a high rate of lethality.

Simon -   Really briefly, are you going to be able to predict in the future what's happening?  It sounds like you're now looking back.  What about the future in under 30 seconds?

Alexei -   So, I think influenza is the main one that we want to predict and it comes every season to New Zealand a new from the airways, landing in Auckland to Christchurch.  So, we also know a huge amount about the molecular structure of that virus and the proteins, how they fold.  So, I think in those cases, we've got huge amounts of data and we know a lot about how the virus actually functions to infect the cells.  We do have chances to predict these things.

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